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Publisher: Elsevier   (Total: 3042 journals)

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Showing 1 - 200 of 3042 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 19, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 16, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 81, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 325, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription  
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 204, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 9, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 22, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 5, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 3)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 123, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 25, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 21, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 24, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 8, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 39, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 40, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 45, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 14)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 12)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 20, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 24)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 34, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 4)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 5, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 21, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 58)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 338, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 6, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 15)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 307, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 7, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 422, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 38, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 50, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 10, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 6)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 6, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 46, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 47, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 44, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 34, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 15, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 30, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 44, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 179, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 54, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 23, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 23, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 33, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 53, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 5)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 160, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 10)
Anesthésie & Réanimation     Full-text available via subscription  
Anesthesiology Clinics     Full-text available via subscription   (Followers: 21, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 152, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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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  [3042 journals]
  • Acknowledgements
    • Authors: Lucio Cocco
      Abstract: Publication date: January 2017
      Source:Advances in Biological Regulation, Volume 63
      Author(s): Lucio Cocco


      PubDate: 2017-02-05T09:26:01Z
      DOI: 10.1016/s2212-4926(17)30018-0
      Issue No: Vol. 63 (2017)
       
  • Casein Kinase II (CK2), Glycogen Synthase Kinase-3 (GSK-3) and Ikaros
           mediated regulation of leukemia
    • Authors: Chandrika Gowda; Mario Soliman; Malika Kapadia; Yali Ding; Kimberly Payne; Sinisa Dovat
      Abstract: Publication date: Available online 6 June 2017
      Source:Advances in Biological Regulation
      Author(s): Chandrika Gowda, Mario Soliman, Malika Kapadia, Yali Ding, Kimberly Payne, Sinisa Dovat
      Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN. More recent data demonstrate another mechanism through which CK2 promotes the PI3K pathway – via transcriptional regulation of PI3K pathway genes by the newly-discovered CK2-Ikaros axis. Together, these data suggest that the CK2 and GSK-3 pathways regulate AKT/PI3K signaling in leukemia via two complementary mechanisms: a) direct phosphorylation of PTEN and b) transcriptional regulation of PI3K-promoting genes. Functional interactions between CK2, Ikaros and GSK3 define a novel signaling network that regulates proliferation of leukemia cells. This regulatory network involves both direct posttranslational modifications (by CK and GSK-3) and transcriptional regulation (via CK2-mediated phosphorylation of Ikaros). This information provides a basis for the development of targeted therapy for leukemia.

      PubDate: 2017-06-16T13:32:08Z
      DOI: 10.1016/j.jbior.2017.06.001
       
  • Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma
    • Authors: Melchiorre Cervello; Giuseppa Augello; Antonella Cusimano; Maria Rita Emma; Daniele Balasus; Antonina Azzolina; James A. McCubrey; Giuseppe Montalto
      Abstract: Publication date: Available online 6 June 2017
      Source:Advances in Biological Regulation
      Author(s): Melchiorre Cervello, Giuseppa Augello, Antonella Cusimano, Maria Rita Emma, Daniele Balasus, Antonina Azzolina, James A. McCubrey, Giuseppe Montalto
      Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3). The roles of GSK-3β in HCC remain controversial, several studies suggested a possible role of GSK-3β as a tumor suppressor gene in HCC, whereas, other studies indicate that GSK-3β is a potential therapeutic target for this neoplasia. In this review, we will focus on the different roles that GSK-3 plays in HCC and its interaction with signaling pathways implicated in the pathogenesis of HCC, such as Insulin-like Growth Factor (IGF), Notch, Wnt/β-catenin, Hedgehog (HH), and TGF-β pathways. In addition, the pivotal roles of GSK3 in epithelial-mesenchymal transition (EMT), invasion and metastasis will be also discussed.

      PubDate: 2017-06-11T13:09:53Z
      DOI: 10.1016/j.jbior.2017.06.002
       
  • Regulation of GSK-3 activity by curcumin, berberine and resveratrol:
           Potential effects on multiple diseases
    • Authors: James McCubrey; Kvin Lertpiriyapong Linda Steelman Steve Abrams Lucio Cocco
      Abstract: Publication date: Available online 26 May 2017
      Source:Advances in Biological Regulation
      Author(s): James A. McCubrey, Kvin Lertpiriyapong, Linda S. Steelman, Steve L. Abrams, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Saverio Candido, Massimo Libra, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus
      Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory processes which may contribute to abnormal proliferation and promote cancer growth. BBR is also isolated from various plants (Berberis coptis and others) and is used in traditional medicine to treat multiple diseases/conditions including: diabetes, hyperlipidemia, cancer and bacterial infections. RES is present in red grapes, other fruits and berries such as blueberries and raspberries. RES may have some anti-diabetic and anti-cancer effects. Understanding the effects of these natural products on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway may enhance their usage as anti-proliferative agent which may be beneficial for many health problems.

      PubDate: 2017-05-27T17:43:11Z
       
  • 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
       
  • Targeting the Akt, GSK-3, Bcl-2 axis in acute myeloid leukemia
    • Authors: Maria Rosaria Ricciardi; Simone Mirabilii; Roberto Licchetta; Monica Piedimonte; Agostino Tafuri
      Abstract: Publication date: Available online 19 May 2017
      Source:Advances in Biological Regulation
      Author(s): Maria Rosaria Ricciardi, Simone Mirabilii, Roberto Licchetta, Monica Piedimonte, Agostino Tafuri
      Over the last few decades, there has been significant progress in the understanding of the pathogenetic mechanisms of the Acute Myeloid Leukemia (AML). However, despite important advances in elucidating molecular mechanisms, the treatment of AML has not improved significantly, remaining anchored at the standard chemotherapy regimen “3 + 7”, with the prognosis of patients remaining severe, especially for the elderly and for those not eligible for transplant procedures. The biological and clinical heterogeneity of AML represents the major obstacle that hinders the improvement of prognosis and the identification of new effective therapeutic approaches. To date, abundant information has been collected on the genetic and molecular alterations of AML carrying prognostic significance. However, not enough is known on how AML progenitors regulate proliferation and survival by redundant and cross-talking signal transduction pathways (STP). Furthermore, it remains unclear how such complicated network affects prognosis and therapeutic treatment options, although many of these molecular determinants are potentially attractive for their druggable characteristics. In this review, some of the key STP frequently deregulated in AML, such as PI3k/Akt/mTOR pathway, GSK3 and components of Bcl-2 family of proteins, are summarized, highlighting in addition their interplay. Based on this information, we reviewed new targeted therapeutic approaches, focusing on the aberrant networks that sustain the AML blast proliferation, survival and drug resistance, aiming to improve disease treatment. Finally, we reported the approaches aimed at disrupting key signaling cross-talk overcoming resistances based on the combination of different targeting therapeutic strategies.

      PubDate: 2017-05-22T17:21:14Z
      DOI: 10.1016/j.jbior.2017.05.002
       
  • GSK-3 as a novel prognostic indicator in leukemia
    • Authors: Peter P. Ruvolo
      Abstract: Publication date: Available online 8 May 2017
      Source:Advances in Biological Regulation
      Author(s): Peter P. Ruvolo
      While leukemias represent a diverse set of diseases with malignant cells derived from myeloid or lymphoid origin, a common feature is the dysregulation of signal transduction pathways that influence leukemogeneisis, promote drug resistance, and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream regulators can activate the AKT kinase which has central roles in supporting cell proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3 (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of metabolism but emerged as central players in cancer in the early 1990s. GSK3 is unique in that the isoforms are constitutively active. Active GSK3 promotes destruction of oncogenic proteins such as beta Catenin, c-MYC, and MCL-1 and thus has tumor suppressor properties. In AML, inactivation of GSK3 is associated with poor overall survival. Interestingly in some leukemias GSK3 targets a tumor suppressor and thus the kinases can act as tumor promoters in those instances. An example is GSK3 targeting p27Kip1 in AML with MLL translocation. This review will cover the role of GSK3 in various leukemias both as tumor suppressor and tumor promoter. We will also briefly cover current state of GSK3 inhibitors for leukemia therapy.

      PubDate: 2017-05-12T16:52:19Z
      DOI: 10.1016/j.jbior.2017.05.001
       
  • Cross-talk between the CK2 and AKT signaling pathways in cancer
    • Authors: Maria Ruzzene; Jessika Bertacchini; Alex Toker; Sandra Marmiroli
      Abstract: Publication date: Available online 28 March 2017
      Source:Advances in Biological Regulation
      Author(s): Maria Ruzzene, Jessika Bertacchini, Alex Toker, Sandra Marmiroli
      CK2 and AKT display a high degree of cross-regulation of their respective functions, both directly, through physical interaction and phosphorylation, and indirectly, through an intense cross-talk of key downstream effectors, ultimately leading to sustained AKT activation. Being CK2 and AKT attractive targets for therapeutic intervention, here we would like to emphasize how AKT and CK2 might influence cell fate through their complex isoform-specific and contextual-dependent cross-talk, to the extent that such functional interplay should be considered when devising therapies that target one or both these key signaling kinases.

      PubDate: 2017-04-03T21:42:14Z
      DOI: 10.1016/j.jbior.2017.03.002
       
  • Inositol phosphate multikinase dependent transcriptional control
    • Authors: Ace J. Hatch; Audrey R. Odom; John D. York
      Abstract: Publication date: Available online 21 March 2017
      Source:Advances in Biological Regulation
      Author(s): Ace J. Hatch, Audrey R. Odom, John D. York
      Production of lipid-derived inositol phosphates including IP4 and IP5 is an evolutionarily conserved process essential for cellular adaptive responses that is dependent on both phospholipase C and the inositol phosphate multikinase Ipk2 (also known as Arg82 and IPMK). Studies of Ipk2, along with Arg82 prior to demonstrating its IP kinase activity, have provided an important link between control of gene expression and IP metabolism as both kinase dependent and independent functions are required for proper transcriptional complex function that enables cellular adaptation in response to extracellular queues such as nutrient availability. Here we define a promoter sequence cis-element, 5′-CCCTAAAAGG-3′, that mediates both kinase-dependent and independent functions of Ipk2. Using a synthetic biological strategy, we show that proper gene expression in cells lacking Ipk2 may be restored through add-back of two components: IP4/IP5 production and overproduction of the MADS box DNA binding protein, Mcm1. Our results are consistent with a mechanism by which Ipk2 harbors a dual functionality that stabilizes transcription factor levels and enzymatically produces a small molecule code, which together coordinate control of biological processes and gene expression.

      PubDate: 2017-03-27T21:21:50Z
      DOI: 10.1016/j.jbior.2017.03.001
       
  • Genomic instability and proliferation/survival pathways in Rb-deficient
           malignancies
    • Authors: Lara Pappas; Xiaoliang Leon Xu; David H. Abramson; Suresh C. Jhanwar
      Abstract: Publication date: Available online 8 February 2017
      Source:Advances in Biological Regulation
      Author(s): Lara Pappas, Xiaoliang Leon Xu, David H. Abramson, Suresh C. Jhanwar
      Genomic instability (GIN) is a hallmark of most cancer cells. However, compared to most human cancer cell types, the retinoblastoma tumor cells show a relatively stable genome. The fundamental basis of this genomic stability has yet to be elucidated, and the role of certain proteins involved in cell cycle regulation may be the key to the development of these specific genotypes. We examined whether thyroid hormone receptor beta 1 and 2 (TRβ1 and TRβ2), known to regulate tumorigenesis, and PTTG1, a mitotic checkpoint protein, play a role in maintaining genomic stability in retinoblastoma. In order to elucidate the role of these proteins in development of aneuploidy/polyploidy, an indicator of GIN, we first studied comparative GIN in retinoblastomas and multiple RB mutant cancer cell lines using single nucleotide polymorphism (SNP) analysis. We then utilized pLKO lentiviral vectors to selectively modify expression of the targeted cell cycle proteins and interpret their effect on downstream cell cycle proteins and their relative effects on the development of polyploidy in multiple tumor cell lines. The SNP analysis showed that retinoblastomas displayed relatively fewer genomic copy number changes as compared to other Rb-deficient cancer cell lines. Both TRβ1 and TRβ2 knockdown led to accumulation of E2F1 and PTTG1 and increased GIN as demonstrated by an increase in polyploidy. Downregulation of PTTG1 led to a relative decrease in GIN while upregulation of PTTG1 led to a relative increase in GIN. Knockdown of E2F1 led to a downstream decrease in PTTG1 expression. RB knockdown also upregulated E2F1 and PTTG1 leading to increased GIN. We showed that RB is necessary for PTTG1 inhibition and genomic stability. A relatively stable genome in retinoblastoma tumor cells is maintained by TRβ1 and TRβ2-mediated PTTG1 inhibition, counteracting RB deficiency-related GIN. TRβ1, TRβ2 and RB KD all led to the downstream PTTG1 accumulation, apparently through an activation of E2F1 resulting in extensive genomic instability as seen in other Rb-deficient tumors.

      PubDate: 2017-02-11T10:39:45Z
      DOI: 10.1016/j.jbior.2017.01.002
       
  • The photograph of PHILIP W. MAJERUS
    • Abstract: Publication date: January 2017
      Source:Advances in Biological Regulation, Volume 63


      PubDate: 2017-02-05T09:26:01Z
       
  • Flimsy Overlay for photograph
    • Abstract: Publication date: January 2017
      Source:Advances in Biological Regulation, Volume 63


      PubDate: 2017-02-05T09:26:01Z
       
  • Photograph of Participants
    • Abstract: Publication date: January 2017
      Source:Advances in Biological Regulation, Volume 63


      PubDate: 2017-02-05T09:26:01Z
       
  • Foreword
    • Authors: Lucio Cocco
      Abstract: Publication date: January 2017
      Source:Advances in Biological Regulation, Volume 63
      Author(s): Lucio Cocco


      PubDate: 2017-02-05T09:26:01Z
       
  • Fhit and Wwox loss-associated genome instability: A genome caretaker
           one-two punch
    • Authors: Morgan S. Schrock; Jenna R. Karras; Matthew J. Guggenbiller; Teresa Druck; Bahadir Batar; Kay Huebner
      Abstract: Publication date: Available online 26 September 2016
      Source:Advances in Biological Regulation
      Author(s): Morgan S. Schrock, Jenna R. Karras, Matthew J. Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
      Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs. As for consequences of Wwox loss in cancer, we show in a small panel of breast cancer cells and mouse embryonic fibroblasts that Wwox expression predicts response to radiation and mitomycin C, all agents that cause DSBs. In addition, loss of Wwox significantly reduced progression free survival in a cohort of ovarian cancer patients treated with platin-based chemotherapies. Finally, stratification of a cohort of squamous lung cancers by Fhit expression reveals that Wwox expression is significantly reduced in the low Fhit-expressing group, suggesting that loss of Fhit is quickly succeeded by loss of Wwox. We propose that Fhit and Wwox loss work synergistically in cancer progression and that DNA damage caused by Fhit could be targeted early in cancer initiation for prevention, while DNA damage caused by Wwox loss could be targeted later in cancer progression, particularly in cancers that develop resistance to genotoxic therapies.

      PubDate: 2017-01-22T08:02:03Z
      DOI: 10.1016/j.jbior.2016.09.008
       
  • Aberrant proteolytic processing and therapeutic strategies in Alzheimer
           disease
    • Authors: Taisuke Tomita
      Abstract: Publication date: Available online 5 January 2017
      Source:Advances in Biological Regulation
      Author(s): Taisuke Tomita
      Amyloid-β peptide (Aβ) and tau are major components of senile plaques and neurofibrillary tangles, respectively, deposited in the brains of Alzheimer disease (AD) patients. Aβ is derived from amyloid-β precursor protein that is sequentially cleaved by two aspartate proteases, β- and γ-secretases. Secreted Aβ is then catabolized by several proteases. Several lines of evidence suggest that accumulation of Aβ by increased production or decreased degradation induces the tau-mediated neuronal toxicity and symptomatic manifestations of AD. Thus, the dynamics of cerebral Aβ, called as “Aβ economy”, would be the mechanistic basis of AD pathogenesis. Partial loss of γ-secretase activity leads to the increased generation of toxic Aβ isoforms, indicating that activation of γ-secretase would provide a beneficial effect for AD. After extensive discovery and development efforts, BACE1, which is a β-secretase enzyme, has emerged as a prime drug target for lowering brain Aβ levels. Recent studies revealed the decreased clearance of Aβ in sporadic AD patients, suggesting the importance of the catabolic mechanism in the pathogenesis of AD. I will discuss with these proteolytic mechanisms involved in the regulation of Aβ economy, and development of effective treatment and diagnostics for AD.

      PubDate: 2017-01-08T06:38:45Z
      DOI: 10.1016/j.jbior.2017.01.001
       
  • Discrete signaling mechanisms of mTORC1 and mTORC2: Connected yet apart in
           cellular and molecular aspects
    • Authors: Meena Jhanwar-Uniyal; Anubhav G. Amin; Jared B. Cooper; Kaushik Das; Meic Schmidt; Raj Murali
      Abstract: Publication date: Available online 4 January 2017
      Source:Advances in Biological Regulation
      Author(s): Meena Jhanwar-Uniyal, Anubhav G. Amin, Jared B. Cooper, Kaushik Das, Meic Schmidt, Raj Murali
      Activation of PI3K/Akt/mTOR (mechanistic target of rapamycin) signaling cascade has been shown in tumorigenesis of numerous malignancies including glioblastoma (GB). This signaling cascade is frequently upregulated due to loss of the tumor suppressor PTEN, a phosphatase that functions antagonistically to PI3K. mTOR regulates cell growth, motility, and metabolism by forming two multiprotein complexes, mTORC1 and mTORC2, which are composed of special binding partners. These complexes are sensitive to distinct stimuli. mTORC1 is sensitive to nutrients and mTORC2 is regulated via PI3K and growth factor signaling. mTORC1 regulates protein synthesis and cell growth through downstream molecules: 4E-BP1 (also called EIF4E-BP1) and S6K. Also, mTORC2 is responsive to growth factor signaling by phosphorylating the C-terminal hydrophobic motif of some AGC kinases like Akt and SGK. mTORC2 plays a crucial role in maintenance of normal and cancer cells through its association with ribosomes, and is involved in cellular metabolic regulation. Both complexes control each other as Akt regulates PRAS40 phosphorylation, which disinhibits mTORC1 activity, while S6K regulates Sin1 to modulate mTORC2 activity. Allosteric inhibitors of mTOR, rapamycin and rapalogs, have essentially been ineffective in clinical trials of patients with GB due to their incomplete inhibition of mTORC1 or unexpected activation of mTOR via the loss of negative feedback loops. Novel ATP binding inhibitors of mTORC1 and mTORC2 suppress mTORC1 activity completely by total dephosphorylation of its downstream substrate pS6KSer235/236, while effectively suppressing mTORC2 activity, as demonstrated by complete dephosphorylation of pAKTSer473. Another significant component of mTORC2 is Sin1, which is crucial for mTORC2 complex formation and function. Furthermore, proliferation and self-renewal of GB cancer stem cells are effectively targetable by these novel mTORC1 and mTORC2 inhibitors. Therefore, the effectiveness of inhibitors of mTOR complexes can be estimated by their ability to suppress both mTORC1 and 2 and their ability to impede both cell proliferation and migration.

      PubDate: 2017-01-08T06:38:45Z
      DOI: 10.1016/j.jbior.2016.12.001
       
  • Sphingolipids in neutrophil function and inflammatory responses:
           Mechanisms and implications for intestinal immunity and inflammation in
           ulcerative colitis
    • Authors: Mel Pilar Espaillat; Richard R. Kew; Lina M. Obeid
      Abstract: Publication date: Available online 14 November 2016
      Source:Advances in Biological Regulation
      Author(s): Mel Pilar Espaillat, Richard R. Kew, Lina M. Obeid
      Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis. In particular, neutrophils are key effector cells and are first line defenders against invading pathogens. While the activity of neutrophils in the intestinal mucosa is required for homeostasis, regulatory mechanisms are equally important to prevent unnecessary activation. In ulcerative colitis, unregulated neutrophil inflammatory mechanisms promote tissue injury and loss of homeostasis. Aberrant neutrophil function represents an early checkpoint in the detrimental cycle of chronic intestinal inflammation; thus, dissecting the mechanisms by which these cells are regulated both before and during disease is essential for understanding the pathogenesis of ulcerative colitis. We present an analysis of the role of sphingolipids in the regulation of neutrophil function and the implication of this relationship in ulcerative colitis.

      PubDate: 2016-11-16T13:57:42Z
      DOI: 10.1016/j.jbior.2016.11.001
       
  • Phospholipid regulation of the nuclear receptor superfamily
    • Authors: Mark K. Crowder; Corey D. Seacrist; Raymond D. Blind
      Abstract: Publication date: Available online 29 October 2016
      Source:Advances in Biological Regulation
      Author(s): Mark K. Crowder, Corey D. Seacrist, Raymond D. Blind
      Nuclear receptors are ligand-activated transcription factors whose diverse biological functions are classically regulated by cholesterol-based small molecules. Over the past few decades, a growing body of evidence has demonstrated that phospholipids and other similar amphipathic molecules can also specifically bind and functionally regulate the activity of certain nuclear receptors, suggesting a critical role for these non-cholesterol-based molecules in transcriptional regulation. Phosphatidylcholines, phosphoinositides and sphingolipids are a few of the many phospholipid like molecules shown to quite specifically regulate nuclear receptors in mouse models, cell lines and in vitro. More recent evidence has also shown that certain nuclear receptors can “present” a bound phospholipid headgroup to key lipid signaling enzymes, which can then modify the phospholipid headgroup with very unique kinetic properties. Here, we review the broad array of phospholipid/nuclear receptor interactions, from the perspective of the chemical nature of the phospholipid, and the cellular abundance of the phospholipid. We also view the data in the light of well established paradigms for phospholipid mediated transcriptional regulation, as well as newer models of how phospholipids might effect transcription in the acute regulation of complex nuclear signaling pathways. Thus, this review provides novel insight into the new, non-membrane associated roles nuclear phospholipids play in regulating complex nuclear events, centered on the nuclear receptor superfamily of transcription factors.

      PubDate: 2016-11-02T13:25:07Z
      DOI: 10.1016/j.jbior.2016.10.006
       
  • Machineries regulating the activity of the small GTPase Arf6 in cancer
           cells are potential targets for developing innovative anti-cancer drugs
    • Authors: Yohei Yamauchi; Yuki Miura; Yasunori Kanaho
      Abstract: Publication date: Available online 18 October 2016
      Source:Advances in Biological Regulation
      Author(s): Yohei Yamauchi, Yuki Miura, Yasunori Kanaho
      The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling.

      PubDate: 2016-11-02T13:25:07Z
      DOI: 10.1016/j.jbior.2016.10.004
       
  • PLC-β1 and cell differentiation: An insight into myogenesis and
           osteogenesis
    • Authors: Giulia Ramazzotti; Irene Faenza; Roberta Fiume; Anna Maria Billi; Lucia Manzoli; Sara Mongiorgi; Stefano Ratti; James A. McCubrey; Pann-Ghill Suh; Lucio Cocco; Matilde Y. Follo
      Abstract: Publication date: Available online 18 October 2016
      Source:Advances in Biological Regulation
      Author(s): Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Anna Maria Billi, Lucia Manzoli, Sara Mongiorgi, Stefano Ratti, James A. McCubrey, Pann-Ghill Suh, Lucio Cocco, Matilde Y. Follo
      Phosphoinositide-phospholipase C-β1 (PLC-β1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation and osteogenesis. During myogenic differentiation of murine C2C12 myoblasts, PLC-β1 signaling pathway involves the Inositol Polyphosphate Multikinase (IPMK) and β-catenin as downstream effectors. By means of c-jun binding to cyclin D3 promoter, the activation of PLC-β1 pathway determines cyclin D3 accumulation. However, osteogenesis requires PLC-β1 expression and up-regulation but it does not affect cyclin D3 levels, suggesting that the two processes require the activation of different mediators.

      PubDate: 2016-11-02T13:25:07Z
      DOI: 10.1016/j.jbior.2016.10.005
       
  • The significance of the 1-kinase/1-phosphatase activities of the PPIP5K
           family
    • Authors: Stephen B. Shears; Brandi M. Baughman; Chunfang Gu; Vasudha S. Nair; Huanchen Wang
      Abstract: Publication date: Available online 17 October 2016
      Source:Advances in Biological Regulation
      Author(s): Stephen B. Shears, Brandi M. Baughman, Chunfang Gu, Vasudha S. Nair, Huanchen Wang
      The inositol pyrophosphates (diphosphoinositol polyphosphates), which include 1-InsP7, 5-InsP7, and InsP8, are highly ‘energetic’ signaling molecules that play important roles in many cellular processes, particularly with regards to phosphate and bioenergetic homeostasis. Two classes of kinases synthesize the PP-InsPs: IP6Ks and PPIP5Ks. The significance of the IP6Ks - and their 5-InsP7 product - has been widely reported. However, relatively little is known about the biological significance of the PPIP5Ks. The purpose of this review is to provide an update on developments in our understanding of key features of the PPIP5Ks, which we believe strengthens the hypothesis that their catalytic activities serve important cellular functions. Central to this discussion is the recent discovery that the PPIP5K is a rare example of a single protein that catalyzes a kinase/phosphatase futile cycle.

      PubDate: 2016-11-02T13:25:07Z
      DOI: 10.1016/j.jbior.2016.10.003
       
  • Ceramidases, roles in sphingolipid metabolism and in health and disease
    • Authors: Nicolas Coant; Wataru Sakamoto; Cungui Mao; Yusuf A. Hannun
      Abstract: Publication date: Available online 11 October 2016
      Source:Advances in Biological Regulation
      Author(s): Nicolas Coant, Wataru Sakamoto, Cungui Mao, Yusuf A. Hannun
      Over the past three decades, extensive research has been able to determine the biologic functions for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P)(Hannun, 1996; Hannun et al., 1986; Okazaki et al., 1989). These studies have managed to define the metabolism, regulation, and function of these bioactive sphingolipids. This emerging body of literature has also implicated bioactive sphingolipids, particularly S1P and ceramide, as key regulators of cellular homeostasis. Ceramidases have the important role of cleaving fatty acid from ceramide and producing sphingosine, thereby controlling the interconversion of these two lipids. Thus far, five human ceramidases encoded by five different genes have been identified: acid ceramidase (AC), neutral ceramidase (NC), alkaline ceramidase 1 (ACER1), alkaline ceramidase 2 (ACER2), and alkaline ceramidase 3 (ACER3). These ceramidases are classified according to their optimal pH for catalytic activity. AC, which is localized to the lysosomal compartment, has been associated with Farber's disease and is involved in the regulation of cell viability. Neutral ceramidase, which is localized to the plasma membrane and primarily expressed in the small intestine and colon, is involved in digestion, and has been implicated in colon carcinogenesis. ACER1 which can be found in the endoplasmic reticulum and is highly expressed in the skin, plays an important role in keratinocyte differentiation. ACER2, localized to the Golgi complex and highly expressed in the placenta, is involved in programed cell death in response to DNA damage. ACER3, also localized to the endoplasmic reticulum and the Golgi complex, is ubiquitously expressed, and is involved in motor coordination-associated Purkinje cell degeneration. This review seeks to consolidate the current knowledge regarding these key cellular players..

      PubDate: 2016-10-13T08:40:17Z
      DOI: 10.1016/j.jbior.2016.10.002
       
  • Roles of TP53 in determining therapeutic sensitivity, growth, cellular
           senescence, invasion and metastasis
    • Authors: James A. McCubrey; Kvin Lertpiriyapong; Timothy L. Fitzgerald; Alberto M. Martelli; Lucio Cocco; Dariusz Rakus; Agnieszka Gizak; Massimo Libra; Melchiorre Cervello; Guiseppe Montalto; Li V. Yang; Stephen L. Abrams; Linda S. Steelman
      Abstract: Publication date: Available online 6 October 2016
      Source:Advances in Biological Regulation
      Author(s): James A. McCubrey, Kvin Lertpiriyapong, Timothy L. Fitzgerald, Alberto M. Martelli, Lucio Cocco, Dariusz Rakus, Agnieszka Gizak, Massimo Libra, Melchiorre Cervello, Guiseppe Montalto, Li V. Yang, Stephen L. Abrams, Linda S. Steelman
      TP53 is a critical tumor suppressor gene that regulates cell cycle progression, apoptosis, cellular senescence and many other properties critical for control of normal cellular growth and death. Due to the pleiotropic effects that TP53 has on gene expression and cellular physiology, mutations at this tumor suppressor gene result in diverse physiological effects. T53 mutations are frequently detected in numerous cancers. The expression of TP53 can be induced by various agents used to treat cancer patients such as chemotherapeutic drugs and ionizing radiation. Radiation will induce Ataxia telangiectasia mutated (ATM) and other kinases that results in the phosphorylation and activation of TP53. TP53 is also negatively regulated by other mechanisms, such as ubiquitination by ligases such as MDM2. While TP53 has been documented to control the expression of many “classical” genes (e.g., p21Cip−1, PUMA, Bax) by transcriptional mechanisms for quite some time, more recently TP53 has been shown to regulate microRNA (miR) gene expression. Different miRs can promote oncogenesis (oncomiR) whereas others act to inhibit tumor progression (tumor suppressor miRs). Targeted therapies to stabilize TP53 have been developed by various approaches, MDM2/MDM4 inhibitors have been developed to stabilize TP53 in TP53-wild type (WT) tumors. In addition, small molecules have been isolated that will reactivate certain mutant TP53s. Both of these types of inhibitors are in clinical trials. Understanding the actions of TP53 may yield novel approaches to suppress cancer, aging and other health problems.

      PubDate: 2016-10-13T08:40:17Z
      DOI: 10.1016/j.jbior.2016.10.001
       
  • Epigenetic regulation of pro-inflammatory cytokine secretion by
           sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase
    • Authors: David L. Ebenezer; Panfeng Fu; Vidyani Suryadevara; Yutong Zhao; Viswanathan Natarajan
      Abstract: Publication date: Available online 29 September 2016
      Source:Advances in Biological Regulation
      Author(s): David L. Ebenezer, Panfeng Fu, Vidyani Suryadevara, Yutong Zhao, Viswanathan Natarajan
      Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. .

      PubDate: 2016-09-30T06:46:02Z
      DOI: 10.1016/j.jbior.2016.09.007
       
  • Biophysical approaches promote advances in the understanding of von
           Willebrand factor processing and function
    • Authors: Achim Löf; Jochen P. Müller; Martin Benoit; Maria A. Brehm
      Abstract: Publication date: Available online 28 September 2016
      Source:Advances in Biological Regulation
      Author(s): Achim Löf, Jochen P. Müller, Martin Benoit, Maria A. Brehm
      The large multimeric plasma glycoprotein von Willebrand factor (VWF) is essential for primary hemostasis by recruiting platelets to sites of vascular injury. VWF multimers respond to elevated hydrodynamic forces by elongation, thereby increasing their adhesiveness to platelets. Thus, the activation of VWF is force-induced, as is its inactivation. Due to these attributes, VWF is a highly interesting system from a biophysical point of view, and is well suited for investigation using biophysical approaches. Here, we give an overview on recent studies that predominantly employed biophysical methods to gain novel insights into multiple aspects of VWF: Electron microscopy was used to shed light on the domain structure of VWF and the mechanism of VWF secretion. High-resolution stochastic optical reconstruction microscopy, atomic force microscopy (AFM), microscale thermophoresis and fluorescence correlation spectroscopy allowed identification of protein disulfide isomerase isoform A1 as the VWF dimerizing enzyme and, together with molecular dynamics simulations, postulation of the dimerization mechanism. Advanced mass spectrometry led to detailed identification of the glycan structures carried by VWF. Microfluidics was used to illustrate the interplay of force and VWF function. Results from optical tweezers measurements explained mechanisms of the force-dependent functions of VWF's domains A1 and A2 and, together with thermodynamic approaches, increased our understanding of mutation-induced dysfunctions of platelet-binding. AFM-based force measurements and AFM imaging enabled exploration of intermonomer interactions and their dependence on pH and divalent cations. These advances would not have been possible by the use of biochemical methods alone and show the benefit of interdisciplinary research approaches.

      PubDate: 2016-09-30T06:46:02Z
      DOI: 10.1016/j.jbior.2016.09.010
       
  • L-plastin regulates the stability of the immune synapse of naive and
           effector T-cells
    • Authors: Guido Wabnitz; Emre Balta; Yvonne Samstag
      Abstract: Publication date: Available online 27 September 2016
      Source:Advances in Biological Regulation
      Author(s): Guido Wabnitz, Emre Balta, Yvonne Samstag
      T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and – vice versa – to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules. We identified glucocorticoid-sensitive phosphorylation of serine 5 on the actin-bundling protein L-plastin as one important signalling event for this regulation. Using imaging flow cytometry as well as confocal and super-resolution microscopy we showed that L-plastin relocalizes to the immune synapse upon antigen encounter, where it associates with the β2-subunit of LFA-1 (CD11a/CD18). Interfering with L-plastin expression or activation leads to a defective LFA-1 recruitment and unstable T-cell/APC contacts. Consequently, the lack of L-plastin diminishes T-cell activation, proliferation and proximal effector responses such as cytokine production. On the other hand, a pro-oxidative milieu leads to prolonged activation of L-plastin resulting in a stronger enrichment of LFA-1 in the cytolytic immune synapse. Concomitant stabilization of conjugates formed by cytotoxic T-cells (CTLs) and their target cells impairs the ability of CTLs to kill more than one target cells (serial killing), which de facto leads to a downregulation of T-cell cytotoxicity. Together, we demonstrate that activation and spacial distribution of L-plastin regulates the maturation and stability of activating and cytolytic immune synapses important for T-cell activation and effector functions.

      PubDate: 2016-09-30T06:46:02Z
      DOI: 10.1016/j.jbior.2016.09.009
       
  • Phospholipase Cγ in Toll-like receptor-mediated inflammation and
           innate immunity
    • Authors: Yoe-Sik Bae; Ha Young Lee; Young Su Jung; Mingyu Lee; Pann-Ghill Suh
      Abstract: Publication date: Available online 27 September 2016
      Source:Advances in Biological Regulation
      Author(s): Yoe-Sik Bae, Ha Young Lee, Young Su Jung, Mingyu Lee, Pann-Ghill Suh
      Among the phospholipase C isoforms, PLCγ not only has unique structural characteristics in terms of harboring SH2 and SH3 domains but also mediates growth factor-induced signaling pathways. PLCγ isoforms are expressed in several innate immune cell types, including macrophages, natural killer cells, mast cells, and neutrophils. Stimulation of Fc receptor or integrin in innate immune cells induces PLCγ activation, which leads to phosphoinositide hydrolysis and calcium increase. The products of PLCγ activity mediate the innate immune response by regulating respiratory burst, phagocytosis, cell adhesion, and cell migration. PLCγ also regulates the inflammatory response by affecting Toll-like receptor-mediated signaling. Here, we briefly review the current understanding of the functional role of PLCγ in inflammation and innate immunity in some innate immune cell types.

      PubDate: 2016-09-30T06:46:02Z
      DOI: 10.1016/j.jbior.2016.09.006
       
  • Diacylglycerol kinases in cancer
    • Authors: Isabel Mérida; Pedro Torres-Ayuso; Antonia Ávila-Flores; Javier Arranz-Nicolás; Elena Andrada; María Tello-Lafoz; Rosa Liébana; Raquel Arcos
      Abstract: Publication date: Available online 23 September 2016
      Source:Advances in Biological Regulation
      Author(s): Isabel Mérida, Pedro Torres-Ayuso, Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, María Tello-Lafoz, Rosa Liébana, Raquel Arcos
      Diacylglycerol kinases (DGK) are a family of enzymes that catalyze the transformation of diacylglycerol into phosphatidic acid. In T lymphocytes, DGKα and ζ limit the activation of the PLCγ/Ras/ERK axis, providing a critical checkpoint to inhibit T cell responses. Upregulation of these isoforms limits Ras activation, leading to hypo-responsive, anergic states similar to those caused by tumors. Recent studies have identified DGKα upregulation in tumor lymphocyte infiltrates, and cells from DGKα and ζ deficient mice show enhanced antitumor activity, suggesting that limitation of DAG based signals by DGK is used by tumors to evade immune attack. DGKα expression is low or even absent in other healthy cells like melanocytes, hepatocytes or neurons. Expression of this isoform, on the other hand, is upregulated in melanoma, hepatocarcinoma and glioblastoma where DGKα contributes to the acquisition of tumor metastatic traits. A model thus emerges where tumor milieu fosters DGKα expression in tumors as well as in tumor infiltrating lymphocytes with opposite consequences. Here we review the mechanism and targets that facilitate tumor “addiction” to DGKα, and discuss its relevance in the more advanced forms of cancer for tumor immune evasion. A better knowledge of this function offers a new perspective in the search for novel approaches to prevent inhibition of immune attack in cancer. Part of the failure in clinical progress may be attributed to the complexity of the tumor/T lymphocyte interaction. As they develop, tumors use a number of mechanisms to drive endogenous, tumor reactive T cells to a general state of hyporesponsiveness or anergy. A better knowledge of the molecular mechanisms that tumors use to trigger T cell anergic states will greatly help in the advance of immunotherapy research.

      PubDate: 2016-09-24T13:16:03Z
      DOI: 10.1016/j.jbior.2016.09.005
       
  • Phosphatidic acid and neurotransmission
    • Authors: Daniel M. Raben; Casey N. Barber
      Abstract: Publication date: Available online 20 September 2016
      Source:Advances in Biological Regulation
      Author(s): Daniel M. Raben, Casey N. Barber
      Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system.

      PubDate: 2016-09-21T13:13:35Z
      DOI: 10.1016/j.jbior.2016.09.004
       
  • Regulation of cellular proliferation in acute lymphoblastic leukemia by
           Casein Kinase II (CK2) and Ikaros
    • Authors: Chandrika Gowda; Chunhua Song; Malika Kapadia; Jonathon L. Payne; Tommy Hu; Yali Ding; Sinisa Dovat
      Abstract: Publication date: Available online 18 September 2016
      Source:Advances in Biological Regulation
      Author(s): Chandrika Gowda, Chunhua Song, Malika Kapadia, Jonathon L. Payne, Tommy Hu, Yali Ding, Sinisa Dovat
      The IKZF1 gene encodes the Ikaros protein, a zinc finger transcriptional factor that acts as a master regulator of hematopoiesis and a tumor suppressor in leukemia. Impaired activity of Ikaros is associated with the development of high-risk acute lymphoblastic leukemia (ALL) with a poor prognosis. The molecular mechanisms that regulate Ikaros' function as a tumor suppressor and regulator of cellular proliferation are not well understood. We demonstrated that Ikaros is a substrate for Casein Kinase II (CK2), an oncogenic kinase that is overexpressed in ALL. Phosphorylation of Ikaros by CK2 impairs Ikaros' DNA-binding ability, as well as Ikaros' ability to regulate gene expression and function as a tumor suppressor in leukemia. Targeting CK2 with specific inhibitors restores Ikaros’ function as a transcriptional regulator and tumor suppressor resulting in a therapeutic, anti-leukemia effect in a preclinical model of ALL. Here, we review the genes and pathways that are regulated by Ikaros and the molecular mechanisms through which Ikaros and CK2 regulate cellular proliferation in leukemia.

      PubDate: 2016-09-21T13:13:35Z
      DOI: 10.1016/j.jbior.2016.09.003
       
  • WANTED – Dead or alive: Myotubularins, a large disease-associated
           protein family
    • Authors: Matthieu A. Raess; Sylvie Friant; Belinda S. Cowling; Jocelyn Laporte
      Abstract: Publication date: Available online 15 September 2016
      Source:Advances in Biological Regulation
      Author(s): Matthieu Raess, Sylvie Friant, Belinda S. Cowling, Jocelyn Laporte
      Myotubularins define a large family of proteins conserved through evolution. Several members are mutated in different neuromuscular diseases including centronuclear myopathies and Charcot-Marie-Tooth (CMT) neuropathies, or are linked to a predisposition to obesity and cancer. While some members have phosphatase activity against the 3-phosphate of phosphoinositides, regulating the phosphorylation status of PtdIns3P and PtdIns(3,5)P 2 implicated in membrane trafficking and autophagy, others lack key residues in the catalytic site and are classified as dead-phosphatases. However, these dead phosphatases regulate phosphoinositide-dependent cellular pathways by binding to catalytically active myotubularins. Here we review previous studies on the molecular regulation and physiological roles of myotubularins. We also used the recent myotubularins three-dimensional structures to underline key residues that are mutated in neuromuscular diseases and required for enzymatic activity and/or regulation. In addition, through database mining and analysis, expression profile and specific isoforms of the different myotubularins are described in depth, as well as a revisited interaction network. Comparison of the interactome and expression data for each myotubularin highlights specific protein complexes and tissues where myotubularins should have a key regulatory role.

      PubDate: 2016-09-15T13:08:24Z
      DOI: 10.1016/j.jbior.2016.09.001
       
  • Rab11 and phosphoinositides: A synergy of signal transducers in the
           control of vesicular trafficking
    • Authors: Carlo Cosimo Campa; Emilio Hirsch
      Abstract: Publication date: Available online 14 September 2016
      Source:Advances in Biological Regulation
      Author(s): Carlo Cosimo Campa, Emilio Hirsch
      Rab11 and phosphoinositides are signal transducers able to direct the delivery of membrane components to the cell surface. Rab11 is a small GTPase that, by cycling from an active to an inactive state, controls key events of vesicular transport, while phosphoinositides are major determinants of membrane identity, modulating compartmentalized small GTPase function. By sharing common effectors, these two signal transducers synergistically direct vesicular traffic to specific intracellular membranes. This review focuses on the latest advances regarding the mechanisms that ensure the compartmentalized regulation of Rab11 function through its interaction with phosphoinositides.

      PubDate: 2016-09-15T13:08:24Z
      DOI: 10.1016/j.jbior.2016.09.002
       
  • Splicing factor gene mutations in the myelodysplastic syndromes: Impact on
           disease phenotype and therapeutic applications
    • Authors: Andrea Pellagatti; Jacqueline Boultwood
      Abstract: Publication date: Available online 21 August 2016
      Source:Advances in Biological Regulation
      Author(s): Andrea Pellagatti, Jacqueline Boultwood
      Splicing factor gene mutations are the most frequent mutations found in patients with the myeloid malignancy myelodysplastic syndrome (MDS), suggesting that spliceosomal dysfunction plays a major role in disease pathogenesis. The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor genes in MDS (SF3B1, SRSF2 and U2AF1) are being identified, illuminating the molecular mechanisms underlying MDS. Emerging data from mouse modelling studies indicate that the presence of splicing factor gene mutations can lead to bone marrow hematopoietic stem/myeloid progenitor cell expansion, impaired hematopoiesis and dysplastic differentiation that are hallmarks of MDS. Importantly, recent evidence suggests that spliceosome inhibitors and splicing modulators may have therapeutic value in the treatment of splicing factor mutant myeloid malignancies.

      PubDate: 2016-08-21T12:06:10Z
      DOI: 10.1016/j.jbior.2016.08.001
       
 
 
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