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BIOLOGY (1469 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 1720 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 21)
Achievements in the Life Sciences     Open Access   (Followers: 5)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 24)
Acta Biologica Colombiana     Open Access   (Followers: 7)
Acta Biologica Hungarica     Full-text available via subscription   (Followers: 4)
Acta Biologica Sibirica     Open Access  
Acta Biomaterialia     Hybrid Journal   (Followers: 27)
Acta Biotheoretica     Hybrid Journal   (Followers: 4)
Acta Chiropterologica     Full-text available via subscription   (Followers: 6)
acta ethologica     Hybrid Journal   (Followers: 4)
Acta Limnologica Brasiliensia     Open Access   (Followers: 3)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Musei Silesiae, Scientiae Naturales : The Journal of Silesian Museum in Opava     Open Access  
Acta Neurobiologiae Experimentalis     Open Access  
Acta Parasitologica     Hybrid Journal   (Followers: 10)
Acta Scientiarum. Biological Sciences     Open Access   (Followers: 2)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
Actualidades Biológicas     Open Access   (Followers: 1)
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advanced Studies in Biology     Open Access  
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Bioinformatics     Open Access   (Followers: 17)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4)
Advances in Biosensors and Bioelectronics     Open Access   (Followers: 7)
Advances in Cell Biology     Open Access   (Followers: 25)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 17)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8)
Advances in High Energy Physics     Open Access   (Followers: 18)
Advances in Human Biology     Open Access   (Followers: 3)
Advances in Life Science and Technology     Open Access   (Followers: 16)
Advances in Life Sciences     Open Access   (Followers: 6)
Advances in Marine Biology     Full-text available via subscription   (Followers: 15)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3)
Advances in Regenerative Biology     Open Access   (Followers: 1)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Virus Research     Full-text available via subscription   (Followers: 5)
African Journal of Range & Forage Science     Hybrid Journal   (Followers: 6)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 1)
Ageing Research Reviews     Hybrid Journal   (Followers: 10)
Aging Cell     Open Access   (Followers: 12)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Agrokreatif Jurnal Ilmiah Pengabdian kepada Masyarakat     Open Access  
AJP Cell Physiology     Full-text available via subscription   (Followers: 14)
AJP Endocrinology and Metabolism     Full-text available via subscription   (Followers: 23)
AJP Lung Cellular and Molecular Physiology     Full-text available via subscription   (Followers: 3)
Al-Kauniyah : Jurnal Biologi     Open Access  
Alasbimn Journal     Open Access   (Followers: 1)
Alces : A Journal Devoted to the Biology and Management of Moose     Open Access  
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Biology Teacher     Full-text available via subscription   (Followers: 14)
American Fern Journal     Full-text available via subscription   (Followers: 1)
American Journal of Agricultural and Biological Sciences     Open Access   (Followers: 8)
American Journal of Bioethics     Hybrid Journal   (Followers: 10)
American Journal of Human Biology     Hybrid Journal   (Followers: 13)
American Journal of Medical and Biological Research     Open Access   (Followers: 8)
American Journal of Plant Sciences     Open Access   (Followers: 18)
American Journal of Primatology     Hybrid Journal   (Followers: 14)
American Malacological Bulletin     Full-text available via subscription   (Followers: 3)
American Naturalist     Full-text available via subscription   (Followers: 70)
Amphibia-Reptilia     Hybrid Journal   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4)
Analytical Methods     Full-text available via subscription   (Followers: 10)
Anatomical Science International     Hybrid Journal   (Followers: 2)
Animal Cells and Systems     Hybrid Journal   (Followers: 4)
Annales de Limnologie - International Journal of Limnology     Hybrid Journal   (Followers: 1)
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3)
Annales UMCS, Biologia     Open Access   (Followers: 1)
Annals of Applied Biology     Hybrid Journal   (Followers: 7)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Human Biology     Hybrid Journal   (Followers: 5)
Annual Review of Biomedical Engineering     Full-text available via subscription   (Followers: 15)
Annual Review of Biophysics     Full-text available via subscription   (Followers: 23)
Annual Review of Cancer Biology     Full-text available via subscription   (Followers: 1)
Annual Review of Cell and Developmental Biology     Full-text available via subscription   (Followers: 37)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 13)
Annual Review of Genomics and Human Genetics     Full-text available via subscription   (Followers: 23)
Annual Review of Phytopathology     Full-text available via subscription   (Followers: 10)
Anthropological Review     Open Access   (Followers: 23)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antibiotics     Open Access   (Followers: 9)
Antioxidants     Open Access   (Followers: 4)
Antioxidants & Redox Signaling     Hybrid Journal   (Followers: 8)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apidologie     Hybrid Journal   (Followers: 4)
Apmis     Hybrid Journal   (Followers: 1)
APOPTOSIS     Hybrid Journal   (Followers: 8)
Applied Bionics and Biomechanics     Open Access   (Followers: 8)
Applied Vegetation Science     Full-text available via subscription   (Followers: 10)
Aquaculture Environment Interactions     Open Access   (Followers: 2)
Aquaculture International     Hybrid Journal   (Followers: 22)
Aquaculture Reports     Open Access   (Followers: 3)
Aquaculture, Aquarium, Conservation & Legislation - International Journal of the Bioflux Society     Open Access   (Followers: 6)
Aquatic Biology     Open Access   (Followers: 5)
Aquatic Ecology     Hybrid Journal   (Followers: 33)
Aquatic Ecosystem Health & Management     Hybrid Journal   (Followers: 14)
Aquatic Science and Technology     Open Access   (Followers: 3)
Aquatic Toxicology     Hybrid Journal   (Followers: 21)
Archaea     Open Access   (Followers: 3)
Archiv für Molluskenkunde: International Journal of Malacology     Full-text available via subscription   (Followers: 3)
Archives of Biological Sciences     Open Access  
Archives of Microbiology     Hybrid Journal   (Followers: 8)
Archives of Natural History     Hybrid Journal   (Followers: 6)
Archives of Oral Biology     Hybrid Journal   (Followers: 2)
Archives of Virology     Hybrid Journal   (Followers: 5)
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Arid Ecosystems     Hybrid Journal   (Followers: 2)
Arquivos do Instituto Biológico     Open Access   (Followers: 1)
Arquivos do Museu Dinâmico Interdisciplinar     Open Access  
Arthropod Structure & Development     Hybrid Journal   (Followers: 2)
Arthropods     Open Access   (Followers: 1)
Artificial DNA: PNA & XNA     Hybrid Journal   (Followers: 3)
Artificial Photosynthesis     Open Access   (Followers: 1)
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Journal of Biodiversity     Open Access   (Followers: 4)
Asian Journal of Biological Sciences     Open Access   (Followers: 3)
Asian Journal of Cell Biology     Open Access   (Followers: 5)
Asian Journal of Developmental Biology     Open Access   (Followers: 2)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 3)
Asian Journal of Nematology     Open Access   (Followers: 4)
Asian Journal of Poultry Science     Open Access   (Followers: 3)
Australian Life Scientist     Full-text available via subscription   (Followers: 2)
Australian Mammalogy     Hybrid Journal   (Followers: 6)
Autophagy     Hybrid Journal   (Followers: 2)
Avian Biology Research     Full-text available via subscription   (Followers: 4)
Avian Conservation and Ecology     Open Access   (Followers: 11)
Bacteriology Journal     Open Access   (Followers: 1)
Bacteriophage     Full-text available via subscription   (Followers: 3)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Plant Taxonomy     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Berita Biologi     Open Access   (Followers: 1)
Between the Species     Open Access   (Followers: 1)
Bio Tribune Magazine     Hybrid Journal  
BIO Web of Conferences     Open Access  
BIO-Complexity     Open Access  
Bio-Grafía. Escritos sobre la Biología y su enseñanza     Open Access  
Bioanalytical Reviews     Hybrid Journal   (Followers: 2)
Biocatalysis and Biotransformation     Hybrid Journal   (Followers: 6)
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 15)
Biochimie     Hybrid Journal   (Followers: 7)
BioControl     Hybrid Journal   (Followers: 5)
Biocontrol Science and Technology     Hybrid Journal   (Followers: 5)
Biodemography and Social Biology     Hybrid Journal  
BioDiscovery     Open Access   (Followers: 2)
Biodiversitas : Journal of Biological Diversity     Open Access  
Biodiversity : Research and Conservation     Open Access   (Followers: 26)
Biodiversity Data Journal     Open Access   (Followers: 3)
Biodiversity Informatics     Open Access   (Followers: 1)
Biodiversity Information Science and Standards     Open Access  
Bioedukasi : Jurnal Pendidikan Biologi FKIP UM Metro     Open Access  
Bioeksperimen : Jurnal Penelitian Biologi     Open Access  
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
Bioenergy Research     Hybrid Journal   (Followers: 2)
Bioengineering and Bioscience     Open Access   (Followers: 1)
BioEssays     Hybrid Journal   (Followers: 10)
Bioethics     Hybrid Journal   (Followers: 14)
BioéthiqueOnline     Open Access  
Biofabrication     Hybrid Journal   (Followers: 5)
Biofilms     Full-text available via subscription   (Followers: 1)
Biogeosciences (BG)     Open Access   (Followers: 10)
Biogeosciences Discussions (BGD)     Open Access   (Followers: 2)
Bioinformatics     Hybrid Journal   (Followers: 291)
Bioinformatics and Biology Insights     Open Access   (Followers: 11)
Bioinspiration & Biomimetics     Hybrid Journal   (Followers: 7)
Biointerphases     Open Access   (Followers: 1)
Biojournal of Science and Technology     Open Access  
Biologia     Hybrid Journal  
Biologia on-line : Revista de divulgació de la Facultat de Biologia     Open Access  
Biological Bulletin     Partially Free   (Followers: 6)
Biological Control     Hybrid Journal   (Followers: 4)
Biological Invasions     Hybrid Journal   (Followers: 18)
Biological Journal of the Linnean Society     Hybrid Journal   (Followers: 18)
Biological Letters     Open Access   (Followers: 5)
Biological Procedures Online     Open Access  
Biological Psychiatry     Hybrid Journal   (Followers: 45)
Biological Psychology     Hybrid Journal   (Followers: 7)
Biological Research     Open Access  
Biological Rhythm Research     Hybrid Journal   (Followers: 2)
Biological Theory     Hybrid Journal   (Followers: 2)
Biological Trace Element Research     Hybrid Journal  
Biologicals     Full-text available via subscription   (Followers: 9)
Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription   (Followers: 1)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 40)
Biologija     Open Access  
Biology     Open Access   (Followers: 3)
Biology and Philosophy     Hybrid Journal   (Followers: 19)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Advances in Biological Regulation
  [SJR: 2.277]   [H-I: 43]   [4 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 2212-4926
   Published by Elsevier Homepage  [3177 journals]
  • Foreword: “Current trends in cancer and signalling”
    • Authors: Pann-Ghill Suh
      Abstract: Publication date: Available online 11 April 2018
      Source:Advances in Biological Regulation
      Author(s): Pann-Ghill Suh

      PubDate: 2018-04-15T17:00:41Z
      DOI: 10.1016/j.jbior.2018.04.001
  • Dual inhibition of PI3K/mTOR signaling in chemoresistant AML primary cells
    • Authors: Jessika Bertacchini; Chiara Frasson; Francesca Chiarini; Daniele D'Avella; Benedetta Accordi; Laura Anselmi; Patrizia Barozzi; Fabio Foghieri; Mario Luppi; Alberto M. Martelli; Giuseppe Basso; Saki Najmaldin; Abbas Khosravi; Fakher Rahim; Sandra Marmiroli
      Abstract: Publication date: Available online 19 March 2018
      Source:Advances in Biological Regulation
      Author(s): Jessika Bertacchini, Chiara Frasson, Francesca Chiarini, Daniele D'Avella, Benedetta Accordi, Laura Anselmi, Patrizia Barozzi, Fabio Foghieri, Mario Luppi, Alberto M. Martelli, Giuseppe Basso, Saki Najmaldin, Abbas Khosravi, Fakher Rahim, Sandra Marmiroli
      A main cause of treatment failure for AML patients is resistance to chemotherapy. Survival of AML cells may depend on mechanisms that elude conventional drugs action and/or on the presence of leukemia initiating cells at diagnosis, and their persistence after therapy. MDR1 gene is an ATP-dependent drug efflux pump known to be a risk factor for the emergence of resistance, when combined to unstable cytogenetic profile of AML patients. In the present study, we analyzed the sensitivity to conventional chemotherapeutic drugs of 26 samples of primary blasts collected from AML patients at diagnosis. Detection of cell viability and apoptosis allowed to identify two group of samples, one resistant and one sensitive to in vitro treatment. The cells were then analyzed for the presence and the activity of P-glycoprotein. A comparative analysis showed that resistant samples exhibited a high level of MDR1 mRNA as well as of P-glycoprotein content and activity. Moreover, they also displayed high PI3K signaling. Therefore, we checked whether the association with signaling inhibitors might resensitize resistant samples to chemo-drugs. The combination showed a very potent cytotoxic effect, possibly through down modulation of MDR1, which was maintained also when primary blasts were co-cultured with human stromal cells. Remarkably, dual PI3K/mTOR inactivation was cytotoxic also to leukemia initiating cells. All together, our findings indicate that signaling activation profiling associated to gene expression can be very useful to stratify patients and improve therapy.

      PubDate: 2018-04-15T17:00:41Z
      DOI: 10.1016/j.jbior.2018.03.001
  • Phosphoinositide 3-kinase pathways and autophagy require
           phosphatidylinositol phosphate kinases
    • Authors: Suyong Choi; Xander Houdek; Richard A. Anderson
      Abstract: Publication date: Available online 8 February 2018
      Source:Advances in Biological Regulation
      Author(s): Suyong Choi, Xander Houdek, Richard A. Anderson
      Phosphatidylinositol phosphate kinases (PIPKs) generate a lipid messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2) that controls essentially all aspects of cellular functions. PI4,5P2 rapidly diffuses in the membrane of the lipid bilayer and does not greatly change in membrane or cellular content, and thus PI4,5P2 generation by PIPKs is tightly linked to its usage in subcellular compartments. Based on this verity, recent study of PI4,5P2 signal transduction has been focused on investigations of individual PIPKs and their underlying molecular regulation of cellular processes. Here, we will discuss recent advances in the study of how PIPKs control specific cellular events through assembly and regulation of PI4,5P2 effectors that mediate specific cellular processes. A focus will be on the roles of PIPKs in control of the phosphoinositide 3-kinase pathway and autophagy.

      PubDate: 2018-02-25T13:03:17Z
      DOI: 10.1016/j.jbior.2018.02.003
  • Application of HTLV-1 tax transgenic mice for therapeutic intervention
    • Authors: Hideki Hasegawa; Kaori Sano; Akira Ainai; Tadaki Suzuki
      Abstract: Publication date: Available online 13 February 2018
      Source:Advances in Biological Regulation
      Author(s): Hideki Hasegawa, Kaori Sano, Akira Ainai, Tadaki Suzuki
      Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by infection of human T-cell leukemia virus type I (HTLV-I). Although the pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy resistance of ATL leads the poor prognosis of this disease. In order to understand the pathogenesis and establish an animal model useful for therapy attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal promoter to restrict the Tax expression in T-cells. The HTLV-1 Tax transgenic mice developed diffuse large-cell lymphomas and leukemia with the similar features of a clinical, pathological and immunological characteristic of acute ATL. The fulminant disease also developed rapidly in SCID mice after engraftment of mouse ATL cells derived from the transgenic mice. In this review, we introduce the therapeutic attempts using this animal model and discuss the possible signaling pathway for a therapeutic target.

      PubDate: 2018-02-15T11:06:49Z
      DOI: 10.1016/j.jbior.2018.02.004
  • Metformin influences drug sensitivity in pancreatic cancer cells
    • Authors: Saverio Candido; Stephen L. Abrams; Linda Steelman; Kvin Lertpiriyapong; Alberto M. Martelli; Lucio Cocco; Stefano Ratti; Matilde Y. Follo; Ramiro M. Murata; Pedro L. Rosalen; Paolo Lombardi; Giuseppe Montalto; Melchiorre Cervello; Agnieszka Gizak; Dariusz Rakus; Pann-Gill Suh; Massimo Libra; James A. McCubrey
      Abstract: Publication date: Available online 12 February 2018
      Source:Advances in Biological Regulation
      Author(s): Saverio Candido, Stephen L. Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M. Martelli, Lucio Cocco, Stefano Ratti, Matilde Y. Follo, Ramiro M. Murata, Pedro L. Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A. McCubrey
      Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes. Metformin acts in part by stimulating AMP-kinase (AMPK) and results in the suppression of mTORC1 activity and the induction of autophagy. In the following studies, we have examined the effects of metformin in the presence of various chemotherapeutic drugs, signal transduction inhibitors and natural products on the growth of three different PDAC lines. Metformin, by itself, was not effective at suppressing growth of the pancreatic cancer cell lines at concentration less than 1000 nM, however, in certain PDAC lines, a suboptimal dose of metformin (250 nM) potentiated the effects of various chemotherapeutic drugs used to treat pancreatic cancer (e.g., gemcitabine, cisplatin, 5-fluorouracil) and other cancer types (e.g., doxorubicin, docetaxel). Furthermore, metformin could increase anti-proliferative effects of mTORC1 and PI3K/mTOR inhibitors as well as natural products such as berberine and the anti-malarial drug chloroquine in certain PDAC lines. Thus, metformin can enhance the effects of certain drugs and signal transduction inhibitors which are used to treat pancreatic and various other cancers.

      PubDate: 2018-02-15T11:06:49Z
      DOI: 10.1016/j.jbior.2018.02.002
  • Acknowledgements
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • Foreword
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • Group photo
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • Key to Group photo
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • Flimsy overlay to Group photo
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • E.Dennis, Special lecturer photo
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-15T11:06:49Z
  • The inflammatory microenvironment that promotes gastrointestinal cancer
           development and invasion
    • Authors: Kanae Echizen; Hiroko Oshima; Mizuho Nakayama; Masanobu Oshima
      Abstract: Publication date: Available online 5 February 2018
      Source:Advances in Biological Regulation
      Author(s): Kanae Echizen, Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
      Accumulating evidence has indicated that the inflammatory response is important for tumor promotion. However, the mechanisms underlying the induction of the inflammatory response in cancer tissues and how it promotes tumorigenesis remain poorly understood. We constructed several mouse models that develop inflammation-associated gastric and intestinal tumors and examined the in vivo mechanisms of tumorigenesis. Of note, the activation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and Toll-like receptor (TLR)/MyD88 signaling cooperatively induced the generation of an inflammatory microenvironment, which is required for early-stage tumorigenesis. The inflammatory response in the stroma induces TNF-α signaling in tumor cells, and the NOX1/ROS signaling pathway is activated downstream. In addition, the inflammatory pathway induces the expression of TLR2 in tumor epithelial cells. Both the NOX1/ROS and TLR2 pathways in tumor cells contribute to the acquisition and maintenance of stemness, which is an important tumor-promoting mechanism stimulated by inflammation. We also found that inflammation promotes malignant processes, like submucosal invasion, of TGF-β signaling-suppressed tumor cells through the activation of MMP2 protease. We also showed that mutant p53 induces innate immune and inflammatory signaling in the tumor stroma by a gain-of-function mechanism of mutant p53, which may explain the “cancer-induced inflammation” mechanism. These results indicate that the regulation of the inflammatory microenvironment via the inhibition of the COX-2/PGE2 and TLR/MyD88 pathways in combination may be an effective preventive or therapeutic strategy against gastrointestinal cancer development and malignant progression, especially those carrying p53 gain-of-function mutations.

      PubDate: 2018-02-05T10:52:45Z
      DOI: 10.1016/j.jbior.2018.02.001
  • Interaction of the Wnt/β-catenin and RAS-ERK pathways involving
           co-stabilization of both β-catenin and RAS plays important roles in the
           colorectal tumorigenesis
    • Authors: Sang-Kyu Lee; Jeong-Ha Hwang; Kang-Yell Choi
      Abstract: Publication date: Available online 10 January 2018
      Source:Advances in Biological Regulation
      Author(s): Sang-Kyu Lee, Jeong-Ha Hwang, Kang-Yell Choi
      Cancer development is usually driven by multiple genetic and molecular alterations rather than by a single defect. In the human colorectal cancer (CRC), series of mutations of genes are involved in the different stages of tumorigenesis. For example, the adenomatous polyposis coli (APC) and KRAS mutations have been known to play roles in the initiation and progression of the tumorigenesis, respectively. However, many studies indicate that mutations of these two genes, which play roles in the Wnt/β-catenin and RAS-extra-cellular signal regulated kinase (ERK) pathways, respectively, cooperatively interact in the tumorigenesis in several different cancer types including CRC. Both Apc and Kras mutations critically increase number and growth rate of tumors although single mutation of these genes did not significantly enhance the small intestinal tumorigenesis of mice. Both APC and KRAS mutations even result in the liver metastasis with inductions of the cancer stem cells (CSCs) markers in a mice xenograft model. In this review, we are going to describe the history for interaction between the Wnt/β-catenin and RAS/ERK pathways especially related with CRC, and provide the mechanical basis for the cross-talk between the two pathways. The highlight of the crosstalk involving the stability regulation of RAS protein via the Wnt/β-catenin signaling which directly related with the cellular proliferation and transformation will be discussed. Activation status of GSK3β, a key enzyme involving both β-catenin and RAS degradations, is regulated by the status of the Wnt/β-catenin signaling dependent upon extracellular stimuli or intracellular abnormalities of the signaling components. The levels of both β-catenin and RAS proteins are co-regulated by the Wnt/β-catenin signaling, and these proteins are overexpressed with a positive correlation in the tumor tissues of CRC patients. These results indicate that the elevation of both β-catenin and RAS proteins is pathologically significant in CRC. In this review, we also will discuss further involvement of the increments of both β-catenin and RAS especially mutant KRAS in the activation of CSCs and metastasis. Overall, the increments of β-catenin and RAS especially mutant KRAS by APC loss play important roles in the corporative tumorigenesis of CRC.

      PubDate: 2018-02-03T10:46:56Z
      DOI: 10.1016/j.jbior.2018.01.001
  • Advances in Biological Regulation
    • Abstract: Publication date: January 2018
      Source:Advances in Biological Regulation, Volume 67

      PubDate: 2018-02-03T10:46:56Z
  • Disrupting the ‘Warburg effect’ re-routes cancer cells to OXPHOS
           offering a vulnerability point via ‘ferroptosis’-induced cell death
    • Authors: Maša Ždralević; Milica Vučetić; Boutaina Daher; Ibtissam Marchiq; Scott K. Parks; Jacques Pouysségur
      Abstract: Publication date: Available online 28 December 2017
      Source:Advances in Biological Regulation
      Author(s): Maša Ždralević, Milica Vučetić, Boutaina Daher, Ibtissam Marchiq, Scott K. Parks, Jacques Pouysségur
      The evolution of life from extreme hypoxic environments to an oxygen-rich atmosphere has progressively selected for successful metabolic, enzymatic and bioenergetic networks through which a myriad of organisms survive the most extreme environmental conditions. From the two lethal environments anoxia/high O2, cells have developed survival strategies through expression of the transcriptional factors ATF4, HIF1 and NRF2. Cancer cells largely exploit these factors to thrive and resist therapies. In this review, we report and discuss the potential therapeutic benefit of disrupting the major Myc/Hypoxia-induced metabolic pathway, also known as fermentative glycolysis or “Warburg effect”, in aggressive cancer cell lines. With three examples of genetic disruption of this pathway: glucose-6-phosphate isomerase (GPI), lactate dehydrogenases (LDHA and B) and lactic acid transporters (MCT1, MCT4), we illuminate how cancer cells exploit metabolic plasticity to survive the metabolic and energetic blockade or arrest their growth. In this context of NRF2 contribution to OXPHOS re-activation we will show and discuss how, by disruption of the cystine transporter xCT (SLC7A11), we can exploit the acute lethal phospholipid peroxidation pathway to induce cancer cell death by ‘ferroptosis’.

      PubDate: 2018-01-03T19:51:58Z
      DOI: 10.1016/j.jbior.2017.12.002
  • Effects of berberine, curcumin, resveratrol alone and in combination with
           chemotherapeutic drugs and signal transduction inhibitors on cancer
           cells—Power of nutraceuticals
    • Authors: James McCubrey; Stephen Abrams Kvin Lertpiriyapong Lucio Cocco Stefano Ratti
      Abstract: Publication date: Available online 3 October 2017
      Source:Advances in Biological Regulation
      Author(s): James A. McCubrey, Stephen L. Abrams, Kvin Lertpiriyapong, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Saverio Candido, Massimo Libra, Ramiro M. Murata, Pedro L. Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Linda S. Steelman
      Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These “healthy” components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/potentials. Understanding the effects of various natural products on cancer cells may enhance their usage as anti-proliferative agents which may be beneficial for many health problems. In this manuscript, we discuss and demonstrate how certain nutraceuticals may enhance other anti-cancer drugs to suppress proliferation of cancer cells.

      PubDate: 2018-01-03T19:51:58Z
  • Regulation of ASK1 signaling by scaffold and adaptor proteins
    • Authors: Lauren Rusnak; Haian Fu
      Pages: 23 - 30
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Lauren Rusnak, Haian Fu
      The mitogen-activated protein kinase (MAPK) signaling pathway is a three-tiered kinase cascade where mitogen-activated protein kinase kinase kinases (MAP3Ks) lead to the activation of mitogen-activated protein kinase kinases (MAP2K), and ultimately MAPK proteins. MAPK signaling can promote a diverse set of biological outcomes, ranging from cell death to proliferation. There are multiple mechanisms which govern MAPK output, such as the duration and strength of the signal, cellular localization to upstream and downstream binding partners, pathway crosstalk and the binding to scaffold and adaptor molecules. This review will focus on scaffold and adaptor proteins that bind to and regulate apoptosis signal-regulating kinase 1 (ASK1), a MAP3K protein with a critical role in mediating stress response pathways.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.003
      Issue No: Vol. 66 (2017)
  • Structural aspects of protein kinase ASK1 regulation
    • Authors: Tomas Obsil; Veronika Obsilova
      Pages: 31 - 36
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Tomas Obsil, Veronika Obsilova
      Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK) signaling cascades in response to various stressors. ASK1 activity is tightly regulated through phosphorylation and interaction with various binding partners. However, the mechanistic details underlying the ASK1 regulation are still not fully understood. This review focuses on recent advances in structural studies of protein kinase ASK1 and on the insights they provide into its mechanism of regulation. In addition, we also discuss protein–protein interactions between ASK1 and its binding partners thioredoxin (TRX) and 14-3-3 protein.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.002
      Issue No: Vol. 66 (2017)
  • ASK family in infection and inflammatory disease
    • Authors: Tomohiko Okazaki
      Pages: 37 - 45
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Tomohiko Okazaki
      Living organisms are continuously exposed to pathogens such as viruses and bacteria. Soon after a limited number of germline-encoded receptors, called pathogen recognition receptors, sense pathogen-associated molecular patterns, hosts trigger innate immune responses, including production of type Ⅰ interferons, proinflammatory cytokines, and cellular apoptosis, to limit propagation of invading pathogens. Importantly, these host responses are also activated during inflammatory diseases, irrespective of pathogen infection, and often play a causal role in pathogenesis and progression of these diseases, thereby implying an intimate link between immune responses and inflammatory disease. The apoptosis signal-regulating kinase (ASK) family belongs to the larger MAP3K family that controls various stress responses. Here, I summarize the critical roles of members of the ASK family during infection and inflammatory disease, and discuss the relationship between these two noxious conditions.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.001
      Issue No: Vol. 66 (2017)
  • Physiological roles of ASK family members in innate immunity and their
           involvement in pathogenesis of immune diseases
    • Authors: Atsushi Matsuzawa
      Pages: 46 - 53
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Atsushi Matsuzawa
      Cells are always exposed to various types of stress, including physical, chemical, and biological stresses, and are required to sense immediately and respond appropriately to these stresses. The apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases, which are activated by not only physicochemical stresses, such as oxidative stress, osmotic pressure, calcium overload, and anti-cancer drugs, but also biological stresses, such as inflammatory cytokines and pathogen infection. Recently, we found that ASK1, a member of ASK family, is activated by bacterial components, such as lipopolysaccharide, in a reactive oxygen species (ROS)-dependent manner, demonstrating that ASK1 is required for the innate immune response and plays a critical role in the regulation of innate immune signaling. Moreover, our findings indicate that ROS are common mediators in physicochemical stress signaling, including redox signaling, and biological stress signaling, including innate immune signaling. This review especially focuses on the roles of ASK family in innate immunity and provides recent progress in our knowledge on activation mechanisms and physiological functions of ASK family kinases in innate immune responses.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.007
      Issue No: Vol. 66 (2017)
  • ASK family in cardiovascular biology and medicine
    • Authors: Tingting Liu; Huanjiao Jenny Zhou; Wang Min
      Pages: 54 - 62
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Tingting Liu, Huanjiao Jenny Zhou, Wang Min
      Cardiovascular disease is a major cause of death worldwide. Mitogen-activated protein kinase (MAPK) signal cascades signaling pathways play crucial roles in cardiovascular pathophysiology. Apoptosis signal-regulating kinase (ASK) family members ASK1, ASK2 and ASK3 are the key molecules in MAPK signal cascades and are activated by various stresses. ASK1 is the most extensively studied MAPKKK and is involved in regulation of the cellular functions such as cell survival, proliferation, inflammation and apoptosis. The current review focuses on the relationship between ASK1 and cardiovascular disease, while exploring the novel therapeutic strategies for cardiovascular disease involved in the ASK1 signal pathway.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.011
      Issue No: Vol. 66 (2017)
  • Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors
    • Authors: Takao Fujisawa
      Pages: 85 - 90
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Takao Fujisawa
      Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an attractive drug target, owing to its essential role in a wide variety of human diseases including neurodegenerative disorders, inflammatory diseases and cancer. Recent studies have suggested that pharmacological manipulations using small molecule ASK1 inhibitors may be beneficial in experimental human disease models. In this review, we highlight the current understanding of ASK1 inhibitors as a potential therapy for human diseases.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.004
      Issue No: Vol. 66 (2017)
  • ASK1 in neurodegeneration
    • Authors: Yuriko Azuchi; Atsuko Kimura; Xiaoli Guo; Goichi Akiyama; Takahiko Noro; Chikako Harada; Atsuko Nishigaki; Kazuhiko Namekata; Takayuki Harada
      Pages: 82 - 87
      Abstract: Publication date: Available online 1 September 2017
      Source:Advances in Biological Regulation
      Author(s): Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Chikako Harada, Takayuki Harada
      Neurodegenerative diseases (NDDs) such as glaucoma, multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are characterized by the progressive loss of neurons, causing irreversible damage to patients. Longer lifespans may be leading to an increase in the number of people affected by NDDs worldwide. Among the pathways strongly impacting the pathogenesis of NDDs, oxidative stress, a condition that occurs because of an imbalance in oxidant and antioxidant levels, has been known to play a vital role in the pathophysiology of NDDs. One of the molecules activated by oxidative stress is apoptosis signal-regulating kinase 1 (ASK1), which has been shown to play a role in NDDs. ASK1 activation is regulated by multiple steps, including oligomerization, phosphorylation, and protein-protein interactions. In the oxidative stress state, reactive oxygen species (ROS) induce the dissociation of thioredoxin, a protein regulating cellular reduction and oxidation (redox), from the N-terminal region of ASK1, and ASK1 is subsequently activated by the oligomerization and phosphorylation of a critical threonine residue, leading to cell death. Here, we review experimental evidence that links ASK1 signaling with the pathogenesis of several NDDs. We propose that ASK1 may be a new point of therapeutic intervention to prevent or treat NDDs.

      PubDate: 2017-09-05T23:02:23Z
      DOI: 10.1016/j.neulet.2016.12.057
      Issue No: Vol. 639 (2017)
  • Remodeling of Ca2+ signaling in cancer: Regulation of inositol
           1,4,5-trisphosphate receptors through oncogenes and tumor suppressors
    • Authors: Hideaki Ando; Katsuhiro Kawaai; Benjamin Bonneau; Katsuhiko Mikoshiba
      Abstract: Publication date: Available online 20 December 2017
      Source:Advances in Biological Regulation
      Author(s): Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
      The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs). Optimal levels of Ca2+ mobilization to mitochondria are necessary for mitochondrial bioenergetics, whereas excessive Ca2+ flux into mitochondria causes loss of mitochondrial membrane integrity and apoptotic cell death. In addition to well-known functions on outer mitochondrial membranes, B-cell lymphoma 2 (Bcl-2) family proteins are localized on the ER and regulate IP3Rs to control Ca2+ transfer into mitochondria. Another regulatory protein of IP3R, IP3R-binding protein released with IP3 (IRBIT), cooperates with or counteracts the Bcl-2 family member depending on cellular states. Furthermore, several oncogenes and tumor suppressors, including Akt, K-Ras, phosphatase and tensin homolog (PTEN), promyelocytic leukemia protein (PML), BRCA1, and BRCA1 associated protein 1 (BAP1), are localized on the ER or at MAMs and negatively or positively regulate apoptotic cell death through interactions with IP3Rs and regulation of Ca2+ dynamics. The remodeling of Ca2+ signaling by oncogenes and tumor suppressors that interact with IP3Rs has fundamental roles in the pathology of cancers.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.12.001
  • Foreword
    • Authors: Hidenori Ichijo
      Abstract: Publication date: December 2017
      Source:Advances in Biological Regulation, Volume 66
      Author(s): Hidenori Ichijo

      PubDate: 2017-12-24T07:37:53Z
  • Forms and functions of store-operated calcium entry mediators, STIM and
    • Authors: James W. Putney
      Abstract: Publication date: Available online 22 November 2017
      Source:Advances in Biological Regulation
      Author(s): James W. Putney
      Calcium signals arise by multiple mechanisms, including mechanisms of release of intracellular stored Ca2+, and the influx of Ca2+ through channels in the plasma membrane. One mechanism that links these two sources of Ca2+ is store-operated Ca2+ entry, the most commonly encountered version of which involves the extensively studied calcium-release-activated Ca2+ (CRAC) channel. The minimal and essential molecular components of the CRAC channel are the STIM proteins that function as Ca2+ sensors in the endoplasmic reticulum, and the Orai proteins that comprise the pore forming subunits of the CRAC channel. CRAC channels are known to play significant roles in a wide variety of physiological functions. This review discusses the multiple forms of STIM and Orai proteins encountered in mammalian cells, and discusses some specific examples of how these proteins modulate or mediate important physiological processes.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.11.006
  • Molecular and cellular mechanisms of chemoresistance in pancreatic cancer
    • Authors: Aleksandra Adamska; Omar Elaskalani; Aikaterini Emmanouilidi; Minkyoung Kim; Norbaini Binti Abdol Razak; Pat Metharom; Marco Falasca
      Abstract: Publication date: Available online 22 November 2017
      Source:Advances in Biological Regulation
      Author(s): Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
      Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients. Nevertheless, gemcitabine remains the standard first-line option for advanced-stage pancreatic cancer patients and, as resistance to the drug has attracted an increasing scientific interest, we deliberate on the main intracellular processes and proteins vital in acquired chemoresistance to gemcitabine. Lastly, our review examines various microenvironmental factors capable of instigating PDAC to develop resistance to chemotherapeutic drugs.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.11.007
  • Normalization of mass spectrometry data (NOMAD)
    • Authors: Carl Murie; Brian Sandri Ann-Sofi Sandberg Timothy Griffin Janne Christine
      Abstract: Publication date: Available online 20 November 2017
      Source:Advances in Biological Regulation
      Author(s): Carl Murie, Brian Sandri, Ann-Sofi Sandberg, Timothy J. Griffin, Janne Lehtiö, Christine Wendt, Ola Larsson
      iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. Such MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, however, that reference normalization does not effectively remove systematic MS run bias. A linear model approach was previously proposed to improve on the reference normalization approach but does not computationally scale to larger data sets. Here we describe the NOMAD (normalization of mass spectrometry data) R package which implements a computationally efficient ANOVA normalization approach with protein assembly functionality. NOMAD provides the same advantages as the linear regression solution but is more computationally efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD effectively removes bias which improves valid across MS run comparisons.

      PubDate: 2017-12-24T07:37:53Z
  • Proliferative and metastatic roles for Phospholipase D in mouse models of
    • Authors: Eric Roth; Michael A. Frohman
      Abstract: Publication date: Available online 14 November 2017
      Source:Advances in Biological Regulation
      Author(s): Eric Roth, Michael A. Frohman
      Phospholipase D (PLD) activity has been proposed to facilitate multiple steps in cancer progression including growth, metabolism, angiogenesis, and mobility. The canonical enzymes PLD1 and PLD2 enact their diverse effects through hydrolyzing the membrane lipid phosphatidylcholine to generate the second messenger and signaling lipid phosphatidic acid (PA). However, the widespread expression of PLD1 and PLD2 in normal tissues and the additional distinct enzymatic mechanisms through which PA can be generated have produced uncertainty regarding the optimal settings in which PLD inhibition might ameliorate cancer. Recent studies in mouse model systems have demonstrated that inhibition or elimination of PLD activity reduces tumor growth and metastasis. One mechanism proposed for this outcome involves proliferative signaling mediated by receptor tyrosine kinases (RTK) and G protein-coupled receptors (GPCR), which is attenuated when downstream PLD signal propagation is suppressed. The reduced proliferative signaling has been reported to be compounded by dysfunctional energetic metabolism in the tumor cells under conditions of nutrient deprivation. Moreover, cancer cells lacking PLD activity display inefficiencies across multiple steps of the metastatic cascade, limiting the tumor's lethal spread. Using PLD isoform knockout mice, recent studies have reported on the net effects of inhibition and ablation in multiple cancer models through examining the role of PLD in the non-tumor cells comprising the stroma and microenvironment. The promising results of such in vivo studies, combined with the apparent low toxicity of highly-specific and potent inhibitors, highlights PLD as an attractive target for therapeutic inhibition in cancer. We discuss here the array of anti-tumor effects produced by PLD inhibition and ablation in cancer models with a focus on animal studies.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.11.004
  • PLCγ1: Potential arbitrator of cancer progression
    • Authors: Hyun-Jun Jang; Pann-Ghill Suh; Yu Jin Lee; Kyeong Jin Shin; Lucio Cocco; Young Chan Chae
      Abstract: Publication date: Available online 8 November 2017
      Source:Advances in Biological Regulation
      Author(s): Hyun-Jun Jang, Pann-Ghill Suh, Yu Jin Lee, Kyeong Jin Shin, Lucio Cocco, Young Chan Chae
      Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca2+) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. PLCγ1, one of the primary subtypes of PLC, is directly activated by membrane receptors, including receptor tyrosine kinases (RTKs), and adhesion receptors such as integrin. PLCγ1 mediates signaling through direct interactions with other signaling molecules via SH domains, as well as its lipase activity. PLCγ1 is frequently enriched and mutated in various cancers, and is involved in the processes of tumorigenesis, including proliferation, migration, and invasion. Although many studies have suggested that PLCγ functions in cell mobility rather than proliferation in cancer, questions remain as to whether PLCγ regulates mitogenesis and whether PLCγ promotes or inhibits proliferation. Moreover, how PLCγ regulates cancer-associated cellular processes and the interplay among other proteins involved in cancer progression have yet to be fully elucidated. In this review, we discuss the current understanding of the role of PLCγ1 in cancer mobility and proliferation.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.11.003
  • Dysregulation of mRNA translation and energy metabolism in cancer
    • Authors: Matthew Leibovitch; Ivan Topisirovic
      Abstract: Publication date: Available online 2 November 2017
      Source:Advances in Biological Regulation
      Author(s): Matthew Leibovitch, Ivan Topisirovic
      Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes. Nonetheless, the role of mTOR and other related signaling nodes (e.g. AMPK) in orchestrating protein synthesis and cancer energetics is only recently being unraveled. In this review, we discuss recent findings that provide insights into the molecular underpinnings of coordination of translational and metabolic programs of cancer cells, and potential strategies to translate these findings into clinical treatments.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.11.001
  • Phospholipase C zeta and calcium oscillations at fertilisation: The
           evidence, applications, and further questions
    • Authors: Junaid Kashir; Michail Nomikos; F. Anthony Lai
      Abstract: Publication date: Available online 27 October 2017
      Source:Advances in Biological Regulation
      Author(s): Junaid Kashir, Michail Nomikos, F. Anthony Lai
      Oocyte activation is a fundamental event at mammalian fertilisation, initiated by a series of characteristic calcium (Ca2+) oscillations in mammals. This characteristic pattern of Ca2+ release is induced in a species-specific manner by a sperm-specific enzyme termed phospholipase C zeta (PLCζ). Reduction or absence of functional PLCζ within sperm underlies male factor infertility in humans, due to mutational inactivation or abrogation of PLCζ protein expression. Underlying such clinical implications, a significant body of evidence has now been accumulated that has characterised the unique biochemical and biophysical properties of this enzyme, further aiding the unique clinical opportunities presented. Herein, we present and discuss evidence accrued over the past decade and a half that serves to support the identity of PLCζ as the mammalian sperm factor. Furthermore, we also discuss the potential novel avenues that have yet to be examined regarding PLCζ mechanism of action in both the oocyte, and the sperm. Finally, we discuss the advances that have been made regarding the clinical therapeutic and diagnostic applications of PLCζ in potentially treating male infertility as a result of oocyte activation deficiency (OAD), and also possibly more general cases of male subfertility.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.012
  • Nuclear inositide signaling and cell cycle
    • Authors: Stefano Ratti; Giulia Ramazzotti; Irene Faenza; Roberta Fiume; Sara Mongiorgi; Anna Maria Billi; James A. McCubrey; Pann-Ghill Suh; Lucia Manzoli; Lucio Cocco; Matilde Y. Follo
      Abstract: Publication date: Available online 23 October 2017
      Source:Advances in Biological Regulation
      Author(s): Stefano Ratti, Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Sara Mongiorgi, Anna Maria Billi, James A. McCubrey, Pann-Ghill Suh, Lucia Manzoli, Lucio Cocco, Matilde Y. Follo
      Phosphatidylinositols (PIs) are responsible for several signaling pathways related to many cellular functions, such as cell cycle regulation at different check-points, cell proliferation, cell differentiation, membrane trafficking and gene expression. PI metabolism is not only present at the cytoplasmic level, but also at the nuclear one, where different signaling pathways affect essential nuclear mechanisms in eukaryotic cells. In this review we focus on nuclear inositide signaling in relation to cell cycle regulation. Many evidences underline the pivotal role of nuclear inositide signaling in cell cycle regulation and cell proliferation associated to different strategic physiopathological mechanisms in several cell systems and diseases.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.008
  • Review of four major distinct types of human phospholipase A2
    • Authors: Alexis M. Vasquez; Varnavas D. Mouchlis; Edward A. Dennis
      Abstract: Publication date: Available online 23 October 2017
      Source:Advances in Biological Regulation
      Author(s): Alexis M. Vasquez, Varnavas D. Mouchlis, Edward A. Dennis
      The phospholipase A2 superfamily of enzymes plays a significant role in the development and progression of numerous inflammatory diseases. Through their catalytic action on membrane phospholipids, phospholipases are the upstream regulators of the eicosanoid pathway releasing free fatty acids for cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes which produce various well-known inflammatory mediators including leukotrienes, thromboxanes and prostaglandins. Elucidating the association of phospholipases A2 with the membrane, the extraction and binding of phospholipid substrates, and their interactions with small-molecule inhibitors is crucial for the development of new anti-inflammatory therapeutics. Studying phospholipases has been challenging because they act on the surface of cellular membranes and micelles. Multidisciplinary approaches including hydrogen/deuterium exchange mass spectrometry, molecular dynamics simulations, and other computer-aided drug design techniques have been successfully employed by our laboratory to study interactions of phospholipases with membranes, phospholipid substrates and inhibitors. This review summarizes the application of these techniques to study four human recombinant phospholipases A2.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.009
  • PIM activity in tumours: A key node of therapy resistance
    • Authors: Richard J. Rebello; Alisée V. Huglo; Luc Furic
      Abstract: Publication date: Available online 22 October 2017
      Source:Advances in Biological Regulation
      Author(s): Richard J. Rebello, Alisée V. Huglo, Luc Furic
      The PIM kinases are proto-oncogenes which have been shown to facilitate cell survival and proliferation to drive malignancy and resistance post-therapy. They are able to suppress cell death signals, sustain PI3K/AKT/mTORC1 pathway activity and regulate the MYC oncogenic program. Recent work has revealed PIM kinase essentiality for advanced tumour maintenance and described tumour sensitivity to small molecule inhibitors targeting PIM kinase in multiple malignancies.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.010
  • Signaling by cell surface death receptors: Alterations in head and neck
    • Authors: Brandon C. Leonard; Daniel E. Johnson
      Abstract: Publication date: Available online 18 October 2017
      Source:Advances in Biological Regulation
      Author(s): Brandon C. Leonard, Daniel E. Johnson
      Cell surface death receptors are members of the tumor necrosis factor receptor (TNFR) superfamily and mediate signals leading to the induction of apoptosis or necroptosis, as well as NF-κB-mediated cell survival. These biochemical processes play key roles in cell growth, development, tissue homeostasis, and immune responses. The downstream signaling complexes activated by different death receptors can differ significantly and are subject to multiple, distinct regulatory mechanisms. Dysregulation of signaling by the TNFR superfamily contributes to a variety of pathologic conditions, including defective immune responses and cancer. Caspase-8 signaling is important for mediating death receptor signals leading to either apoptosis or NF-κB activation. By contrast, inactivation of caspase-8 or loss of caspase-8 expression shifts death receptor signaling to the necroptosis pathway. Notably, the gene encoding caspase-8 is mutated in roughly ten percent of head and neck cancers. These findings support the hypothesis that alterations in the biochemical pathways mediated by death receptors have important consequences for the development of head and neck, and possibly other, cancers.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.006
  • Sphingosine kinase 1 in breast cancer
    • Authors: Kurt Geffken; Sarah Spiegel
      Abstract: Publication date: Available online 16 October 2017
      Source:Advances in Biological Regulation
      Author(s): Kurt Geffken, Sarah Spiegel
      Breast cancer affects 1 out of 8 women in the US and is the second highest cause of death from cancer for women, leading to considerable research examining the causes, progression, and treatment of breast cancer. Over the last two decades, sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes important for breast cancer including growth, progression, transformation and metastasis, and is the focus of this review. In particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1), has come under increasing scrutiny as it is commonly upregulated in breast cancer cells and has been linked with poorer prognosis and progression, possibly leading to resistance to certain anti-cancer therapies. In this review, we will also discuss preclinical studies of both estrogen receptor (ER) positive as well as triple-negative breast cancer mouse models with inhibitors of SphK1 and other compounds that target the S1P axis and have shown good promise in reducing tumor growth and metastasis. It is hoped that in the future this will lead to development of novel combination approaches for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.

      PubDate: 2017-12-24T07:37:53Z
      DOI: 10.1016/j.jbior.2017.10.005
  • The importance of blood platelet lipid signaling in thrombosis and in
    • Authors: Fanny Vardon Bounes; Abdulrahman Mujalli; Claire Cenac; Sonia Severin; Pauline Lefaouder; Gaëtan Chicanne; Frédérique Gaits-Iacovoni; Vincent Minville; Marie-Pierre Gratacap; Bernard Payrastre
      Abstract: Publication date: Available online 29 September 2017
      Source:Advances in Biological Regulation
      Author(s): Fanny Vardon Bounes, Abdulrahman Mujalli, Claire Cenac, Sonia Severin, Pauline Le Faouder, Gaëtan Chicanne, Frédérique Gaits-Iacovoni, Vincent Minville, Marie-Pierre Gratacap, Bernard Payrastre
      Blood platelets are the first line of defense against hemorrhages and are also strongly involved in the processes of arterial thrombosis, a leading cause of death worldwide. Besides their well-established roles in hemostasis, vascular wall repair and thrombosis, platelets are now recognized as important players in other processes such as inflammation, healing, lymphangiogenesis, neoangiogenesis or cancer. Evidence is accumulating they are key effector cells in immune and inflammatory responses to host infection. To perform their different functions platelets express a wide variety of membrane receptors triggering specific intracellular signaling pathways and largely use lipid signaling systems. Lipid metabolism is highly active in stimulated platelets including the phosphoinositide metabolism with the phospholipase C (PLC) and the phosphoinositide 3-kinase (PI3K) pathways but also other enzymatic systems producing phosphatidic acid, lysophosphatidic acid, platelet activating factor, sphingosine 1-phosphate and a number of eicosanoids. While several of these bioactive lipids regulate intracellular platelet signaling mechanisms others are released by activated platelets acting as autocrine and/or paracrine factors modulating neighboring cells such as endothelial and immune cells. These bioactive lipids have been shown to play important roles in hemostasis and thrombosis but also in vessel integrity and dynamics, inflammation, tissue remodeling and wound healing. In this review, we will discuss some important aspects of platelet lipid signaling in thrombosis and during sepsis that is an important cause of death in intensive care unit. We will particularly focus on the implication of the different isoforms of PI3Ks and on the generation of eicosanoids released by activated platelets.

      PubDate: 2017-10-06T23:46:57Z
      DOI: 10.1016/j.jbior.2017.09.011
  • DGKζ ablation engenders upregulation of p53 level in the spleen upon
           whole-body ionizing radiation
    • Authors: Toshiaki Tanaka; Ken Iseki; Ken Tanaka; Tomoyuki Nakano; Mitsuyoshi Iino; Kaoru Goto
      Abstract: Publication date: Available online 28 September 2017
      Source:Advances in Biological Regulation
      Author(s): Toshiaki Tanaka, Ken Iseki, Ken Tanaka, Tomoyuki Nakano, Mitsuyoshi Iino, Kaoru Goto
      The tumor suppressor gene product p53, which coordinates the cellular response to various stresses, is subject to tight regulation by a complex network of signal transduction. The DGK family metabolizes lipidic second messenger diacylglycerol to produce phosphatidic acid. Our earlier studies showed that one isozyme, DGKζ, is involved in the regulatory mechanism of p53. In a cellular model of doxorubicin-induced DNA damage, overexpression of wild-type DGKζ suppresses p53 protein induction and reduces apoptosis, whereas knockdown of DGKζ upregulates p53 protein level and promotes apoptosis. Further examination reveals that DGKζ facilitates p53 degradation via ubiquitin-proteasome system in the cytoplasm. However, it remains undetermined whether the regulatory mechanism of DGKζ on p53 function found in cell-based experiments is also functional at the animal level. This study was conducted to elucidate this point using an experiment with DGKζ-KO mice under DNA damage induced by whole-body ionizing radiation. Our results reveal that p53 protein is induced robustly in the spleen of DGKζ-KO mice upon exposure to ionizing radiation, thereby promoting apoptosis in this organ. Taken together, the results demonstrate that DGKζ plays a sentinel role in p53 expression at the cellular and organismal levels after DNA damaging stress conditions.

      PubDate: 2017-09-28T23:19:25Z
      DOI: 10.1016/j.jbior.2017.09.010
  • Splicing factor mutations in the myelodysplastic syndromes: Target genes
           and therapeutic approaches
    • Authors: Richard N. Armstrong; Violetta Steeples; Shalini Singh; Andrea Sanchi; Jacqueline Boultwood; Andrea Pellagatti
      Abstract: Publication date: Available online 22 September 2017
      Source:Advances in Biological Regulation
      Author(s): Richard N. Armstrong, Violetta Steeples, Shalini Singh, Andrea Sanchi, Jacqueline Boultwood, Andrea Pellagatti
      Mutations in splicing factor genes (SF3B1, SRSF2, U2AF1 and ZRSR2) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology. These findings have led to the development of therapeutic strategies using splicing-modulating agents and rapid progress is being made in this field. Splicing inhibitors are promising agents that exploit the preferential sensitivity of splicing factor-mutant cells to these compounds. Here, we review the known target genes associated with splicing factor mutations in MDS, and discuss the potential of splicing-modulating therapies for these disorders.

      PubDate: 2017-09-22T23:14:37Z
      DOI: 10.1016/j.jbior.2017.09.008
  • Microbial inositol polyphosphate metabolic pathway as drug development
    • Authors: Adolfo Saiardi; Cristina Azevedo; Yann Desfougères; Paloma Portela-Torres; Miranda S.C. Wilson
      Abstract: Publication date: Available online 22 September 2017
      Source:Advances in Biological Regulation
      Author(s): Adolfo Saiardi, Cristina Azevedo, Yann Desfougères, Paloma Portela-Torres, Miranda S.C. Wilson
      Inositol polyphosphates are a diverse and multifaceted class of intracellular messengers omnipresent in eukaryotic cells. These water-soluble molecules regulate many aspects of fundamental cell physiology. Removing this metabolic pathway is deleterious: inositol phosphate kinase null mutations can result in lethality or substantial growth phenotypes. Inositol polyphosphate synthesis occurs through the actions of a set of kinases that phosphorylate phospholipase-generated IP3 to higher phosphorylated forms, such as the fully phosphorylated IP6 and the inositol pyrophosphates IP7 and IP8. Unicellular organisms have a reduced array of the kinases for synthesis of higher phosphorylated inositol polyphosphates, while human cells possess two metabolic routes to IP6. The enzymes responsible for inositol polyphosphate synthesis have been identified in all eukaryote genomes, although their amino acid sequence homology is often barely detectable by common search algorithms. Homology between human and microbial inositol phosphate kinases is restricted to a few catalytically important residues. Recent studies of the inositol phosphate metabolic pathways in pathogenic fungi (Cryptococcus neoformans) and protozoa (Trypanosome brucei) have revealed the importance of the highly phosphorylated inositol polyphosphates to the fitness and thus virulence of these pathogens. Given this, identification of inositol kinase inhibitors specifically targeting the kinases of pathogenic microorganisms is desirable and achievable.

      PubDate: 2017-09-22T23:14:37Z
      DOI: 10.1016/j.jbior.2017.09.007
  • MYO18A: An unusual myosin
    • Authors: Matthew D. Buschman; Seth J. Field
      Abstract: Publication date: Available online 18 September 2017
      Source:Advances in Biological Regulation
      Author(s): Matthew D. Buschman, Seth J. Field
      MYO18A is a divergent member of the myosin family characterized by the presence of an amino-terminal PDZ domain. MYO18A has been found in a few different complexes involved in intracellular transport processes. MYO18A is found in a complex with LURAP1 and MRCK that functions in retrograde treadmilling of actin. It also has been found in a complex with PAK2, βPIX, and GIT1, functioning to transport that protein complex from focal adhesions to the leading edge. Finally, a high proportion of MYO18A is found in complex with GOLPH3 at the trans Golgi, where it functions to promote vesicle budding for Golgi-to-plasma membrane trafficking. Interestingly, MYO18A has been implicated as a cancer driver, as have other components of the GOLPH3 pathway. It remains uncertain as to whether or not MYO18A has intrinsic motor activity. While many questions remain, MYO18A is a fascinatingly unique myosin that is essential in higher organisms.

      PubDate: 2017-09-22T23:14:37Z
      DOI: 10.1016/j.jbior.2017.09.005
  • Where do substrates of diacylglycerol kinases come from'
           Diacylglycerol kinases utilize diacylglycerol species supplied from
           phosphatidylinositol turnover-independent pathways
    • Authors: Fumio Sakane; Satoru Mizuno; Daisuke Takahashi; Hiromichi Sakai
      Abstract: Publication date: Available online 9 September 2017
      Source:Advances in Biological Regulation
      Author(s): Fumio Sakane, Satoru Mizuno, Daisuke Takahashi, Hiromichi Sakai
      Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Mammalian DGK comprises ten isozymes (α–κ) and regulates a wide variety of physiological and pathological events, such as cancer, type II diabetes, neuronal disorders and immune responses. DG and PA consist of various molecular species that have different acyl chains at the sn-1 and sn-2 positions, and consequently, mammalian cells contain at least 50 structurally distinct DG/PA species. Because DGK is one of the components of phosphatidylinositol (PI) turnover, the generally accepted dogma is that all DGK isozymes utilize 18:0/20:4-DG derived from PI turnover. We recently established a specific liquid chromatography-mass spectrometry method to analyze which PA species were generated by DGK isozymes in a cell stimulation-dependent manner. Interestingly, we determined that DGKδ, which is closely related to the pathogenesis of type II diabetes, preferentially utilized 14:0/16:0-, 14:0/16:1-, 16:0/16:0-, 16:0/16:1-, 16:0/18:0- and 16:0/18:1-DG species (X:Y = the total number of carbon atoms: the total number of double bonds) supplied from the phosphatidylcholine-specific phospholipase C pathway, but not 18:0/20:4-DG, in high glucose-stimulated C2C12 myoblasts. Moreover, DGKα mainly consumed 14:0/16:0-, 16:0/18:1-, 18:0/18:1- and 18:1/18:1-DG species during cell proliferation in AKI melanoma cells. Furthermore, we found that 16:0/16:0-PA was specifically produced by DGKζ in Neuro-2a cells during retinoic acid- and serum starvation-induced neuronal differentiation. These results indicate that DGK isozymes utilize a variety of DG molecular species derived from PI turnover-independent pathways as substrates in different stimuli and cells. DGK isozymes phosphorylate various DG species to generate various PA species. It was revealed that the modes of activation of conventional and novel protein kinase isoforms by DG molecular species varied considerably. However, PA species-selective binding proteins have not been found to date. Therefore, we next attempted to identify PA species-selective binding proteins from the mouse brain and identified α-synuclein, which has causal links to Parkinson's disease. Intriguingly, we determined that among phospholipids, including several PA species (16:0/16:0-PA, 16:0/18:1-PA, 18:1/18:1-PA, 18:0/18:0-PA and 18:0/20:4-PA); 18:1/18:1-PA was the most strongly bound PA to α-synuclein. Moreover, 18:1/18:1-PA strongly enhanced secondary structural changes from the random coil form to the α-helix form and generated a multimeric and proteinase K-resistant α-synuclein protein. In contrast with the dogma described above, our recent studies strongly suggest that PI turnover-derived DG species and also various DG species derived from PI turnover-independent pathways are utilized by DGK isozymes. DG species supplied from distinct pathways may be utilized by DGK isozymes based on different stimuli present in different types of cells, and individual PA molecular species would have specific targets and exert their own physiological functions.

      PubDate: 2017-09-11T23:07:13Z
      DOI: 10.1016/j.jbior.2017.09.003
  • Phospholipase Cβ interacts with cytosolic partners to regulate cell
    • Authors: Suzanne Scarlata; Ashima Singla; Osama Garwain
      Abstract: Publication date: Available online 9 September 2017
      Source:Advances in Biological Regulation
      Author(s): Suzanne Scarlata, Ashima Singla, Osama Garwain
      Phospholipase Cβ (PLCβ) is the main effector of the Gαq signaling pathway relaying different extracellular sensory information to generate intracellular calcium signals. Besides this classic function, we have found that PLCβ plays an important but unknown role in regulating PC12 cell differentiation by interacting with components in the RNA-induced silencing machinery. In trying to understand the role of PLCβ in PC12 cell differentiation, we find that over-expressing PLCβ reduces PC12 cell proliferation while down-regulating PLCβ increases the rate of cell proliferation. However, this behavior is not seen in other cancerous cell lines. To determine the underlying mechanism, we carried out mass spectrometry analysis of PLCβ complexes in PC12 cells. We find that in unsynchronized cells, PLCβ primarily binds cyclin-dependent kinase (CDK) 16 whose activity plays a key role in cell proliferation. In vitro studies show a direct association between the two proteins that result in loss in CKD16 activity. When cells are arrested in the G2/M phase, a large population of PLCβ is bound to Ago2 in a complex that contains C3PO and proteins commonly found in stress granules. Additionally, another population of PLCβ complexes with CDK18 and cyclin B1. Fluorescence lifetime imaging microscopy (FLIM) confirms cell cycle dependent associations between PLCβ and these other protein binding partners. Taken together, our studies suggest that PLCβ may play an active role in mediating interactions required to move through the cell cycle.

      PubDate: 2017-09-11T23:07:13Z
      DOI: 10.1016/j.jbior.2017.09.004
  • Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome
    • Authors: Alan J. Warren
      Abstract: Publication date: Available online 6 September 2017
      Source:Advances in Biological Regulation
      Author(s): Alan J. Warren
      Mutations that target the ubiquitous process of ribosome assembly paradoxically cause diverse tissue-specific disorders (ribosomopathies) that are often associated with an increased risk of cancer. Ribosomes are the essential macromolecular machines that read the genetic code in all cells in all kingdoms of life. Following pre-assembly in the nucleus, precursors of the large 60S and small 40S ribosomal subunits are exported to the cytoplasm where the final steps in maturation are completed. Here, I review the recent insights into the conserved mechanisms of ribosome assembly that have come from functional characterisation of the genes mutated in human ribosomopathies. In particular, recent advances in cryo-electron microscopy, coupled with genetic, biochemical and prior structural data, have revealed that the SBDS protein that is deficient in the inherited leukaemia predisposition disorder Shwachman-Diamond syndrome couples the final step in cytoplasmic 60S ribosomal subunit maturation to a quality control assessment of the structural and functional integrity of the nascent particle. Thus, study of this fascinating disorder is providing remarkable insights into how the large ribosomal subunit is functionally activated in the cytoplasm to enter the actively translating pool of ribosomes.

      PubDate: 2017-09-11T23:07:13Z
      DOI: 10.1016/j.jbior.2017.09.002
  • Phosphoinositide 5-phosphatase activities control cell motility in
           glioblastoma: Two phosphoinositides PI(4,5)P2 and PI(3,4)P2 are involved
    • Authors: Ana Raquel Ramos; William's Elong Edimo; Christophe Erneux
      Abstract: Publication date: Available online 5 September 2017
      Source:Advances in Biological Regulation
      Author(s): Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
      Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes. Protein kinase B is one target protein and activation of the kinase will have a major impact on cell proliferation, survival and cell metabolism. Two other PIs, PI(4,5)P2 and PI(3,4)P2, are produced or used as substrates of PI 5-phosphatases (OCRL, INPP5B, SHIP1/2, SYNJ1/2, INPP5K, INPP5J, INPP5E). The inositol lipids may influence many aspects of cytoskeletal organization, lamellipodia formation and F-actin polymerization. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in cancer cells. In glioblastoma, reducing SHIP2 expression can positively or negatively affect the speed of cell migration depending on the glioblastoma cell type. The two PI 5-phosphatases SHIP2 or SKIP could be localized at the plasma membrane and can reduce either PI(3,4,5)P3 or PI(4,5)P2 abundance. In the glioblastoma 1321 N1 cells, SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration.

      PubDate: 2017-09-05T23:02:23Z
      DOI: 10.1016/j.jbior.2017.09.001
  • Phosphatidate phosphatase regulates membrane phospholipid synthesis via
           phosphatidylserine synthase
    • Authors: George M. Carman; Gil-Soo Han
      Abstract: Publication date: Available online 16 August 2017
      Source:Advances in Biological Regulation
      Author(s): George M. Carman, Gil-Soo Han
      The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the synthesis of triacylglycerol. The CHO1-encoded phosphatidylserine synthase, which catalyzes the committed step in membrane phospholipid synthesis via CDP-diacylglycerol, and the PAH1-encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced synthesis of membrane phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1Δ mutation) increases the level of phosphatidate and its conversion to membrane phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UASINO), a cis-acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates phospholipid synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme.

      PubDate: 2017-08-23T22:22:17Z
      DOI: 10.1016/j.jbior.2017.08.001
  • The regulatory and signaling mechanisms of the ASK family
    • Authors: Takuto Nishida; Kazuki Hattori; Kengo Watanabe
      Abstract: Publication date: Available online 22 May 2017
      Source:Advances in Biological Regulation
      Author(s): Takuto Nishida, Kazuki Hattori, Kengo Watanabe
      Apoptosis signal-regulating kinase 1 (ASK1) was identified as a MAP3K that activates the JNK and p38 pathways, and subsequent studies have reported ASK2 and ASK3 as members of the ASK family. The ASK family is activated by various intrinsic and extrinsic stresses, including oxidative stress, ER stress and osmotic stress. Numerous lines of evidence have revealed that members of the ASK family are critical for signal transduction systems to control a wide range of stress responses such as cell death, differentiation and cytokine induction. In this review, we focus on the precise signaling mechanisms of the ASK family in response to diverse stressors.

      PubDate: 2017-05-22T17:21:14Z
      DOI: 10.1016/j.jbior.2017.05.004
  • ASK family and cancer
    • Authors: Hiroki Ryuno; Isao Naguro; Miki Kamiyama
      Abstract: Publication date: Available online 20 May 2017
      Source:Advances in Biological Regulation
      Author(s): Hiroki Ryuno, Isao Naguro, Miki Kamiyama
      Cancer is a major problem in public health and is one of the leading causes of mortality worldwide. Many types of cancer cells exhibit aberrant cellular signal transduction in response to stress, which often leads to oncogenesis. Mitogen-activated protein kinase (MAPK) signal cascades are one of the important intracellular stress signaling pathways closely related to cancer. The key molecules in MAPK signal cascades that respond to various types of stressors are apoptosis signal-regulating kinase (ASK) family members; ASK1, ASK2 and ASK3. ASK family members are activated by a wide variety of stressors, and they regulate various cellular responses, such as cell proliferation, inflammation and apoptosis. In this review, we will discuss both the oncogenic and anti-oncogenic roles of the ASK family members in various contexts of cancer development with deeper insights into the involvement of ASK family members in cancer pathology.

      PubDate: 2017-05-22T17:21:14Z
      DOI: 10.1016/j.jbior.2017.05.003
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