Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH): The Quintessential Moonlighting Protein in Normal Cell Function and in Human Disease examines the biochemical protein interactions of the multi-dimensional protein GAPDH, further considering the regulatory mechanisms through which cells control their functional diversity.
This protein’s diverse activities range from nuclear tRNA export and the maintenance of genomic integrity, to cytoplasmic post-transcriptional control of gene expression and receptor mediated cell signaling, to membrane facilitation of iron metabolism, trafficking and fusion.
This book will be of great interest to basic scientists, clinicians and students, including molecular and cell biologists, immunologists, pathologists and clinical researchers who are interested in the biochemistry of GAPDH in health and disease.
- Contextualizes how GAPDH is utilized by cells in vivo
- Provides detailed insight into GAPDH post-translational modifications, including functional diversity and its subcellular localization
- Includes forward-thinking exposition on tough topics, such as the exploration of how GAPDG performs functions, how it decides where it should be present and requisite structural requirements
Graduate students, postdoctoral fellows, and established researchers interested in biochemistry, molecular biology, cell biology, immunology, and pathology
Section I. Moonlighting GAPDH in Normal Cell Function
1. Transcriptional Expression
2. Post-translational mRNA Regulation
3. Iron Metabolism
4. Membrane Trafficking
5. Maintenance of DNA Integrity
6. GAPDH and Neural Transmission
7. GAPDH and Cell Proliferation
Section II. Physiological Stress and GAPDH Functional Diversity
1. GAPDH and Oxidative Stress: Nitric Oxide, apoptosis and heme metabolism
2. GAPDH and Hypoxia
3. GAPDH and Ischemia. Ischemia may be defined as a restriction in blood supply to tissues resulting in oxygen deprivation. Recent studies indicate that moonlighting GAPDH may be specifically regulated as a function of ischemic stress. This includes its role in receptor mediated glutamate exocytosis and its intracellular interaction with the p53 protein. The former regulates AMPAR action while the latter involves the formation of a GAPDH:p53 protein-protein complex as well as post-translational modification of the p53 protein.
Section III. The Pathology of GAPDH Functional Diversity
1. GAPDH and Age-Related Neurodegenerative Disease
2. Moonlighting GAPDH and Cancer Development
3. Functional Diversity of GAPDH in Infection and Immunity
Section IV. The Pharmacology of Moonlighting GAPDH
Section V. Discussion
- No. of pages:
- © Academic Press 2017
- 25th May 2017
- Academic Press
- eBook ISBN:
- Paperback ISBN:
Michael A. Sirover, Ph.D., is a Professor of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA. He received his B.S. in Biology from Rensselaer Polytechnic Institute, his Ph.D. from the State University of New York at Stony Brook and was a postdoctoral fellow at the Fox Chase Cancer Center in Philadelphia. He was an Associate Editor of the journal Cancer Research and, for over a decade, was the Chair of a National Cancer Institute Special Advisory Committee on Cancer Prevention. Dr. Sirover is one of the pioneers in the identification and characterization of multifunctional proteins. His early work on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) helped establish it as the prime example of this new class of cell proteins. His studies focused on its proliferative dependent regulation, including distinctive changes in its subcellular localization as a function of the cell cycle, its proliferative-dependent transcriptional and translational regulation, its role in DNA repair, the pathology of age-related neurodegenerative disease and the cellular phenotype of Bloom’s syndrome, a cancer protein human genetic disorder. He isolated and characterized anti-GAPDH monoclonal antibodies and the human GAPDH gene, each of which were subsequently used by many other researchers in their individual GAPDH studies. Lastly, he is the author of the definitive reviews of GAPDH structure and function as well as its role in the pathology of human disease.
Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA