Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)

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.

Section I. Moonlighting GAPDH in Normal Cell Function1. Transcriptional Expression2. Post-translational mRNA Regulation3. Iron Metabolism4. Membrane Trafficking5. Maintenance of DNA Integrity6. GAPDH and Neural Transmission7. GAPDH and Cell Proliferation

Section II. Physiological Stress and GAPDH Functional Diversity1. GAPDH and Oxidative Stress: Nitric Oxide, apoptosis and heme metabolism2. GAPDH and Hypoxia3. 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 Diversity1. GAPDH and Age-Related Neurodegenerative Disease2. Moonlighting GAPDH and Cancer Development3. Functional Diversity of GAPDH in Infection and Immunity

Section IV. The Pharmacology of Moonlighting GAPDH

Section V. Discussion