ROLE OF THE GLYCOLYTIC PROTEIN, GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, IN NORMAL-CELL FUNCTION AND IN CELL PATHOLOGY

The glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH ) appeared to be an archtypical protein of limited excitement. However , independent studies from a number of different laboratories reported a variety of diverse biological properties of the GAPDH protein. As a membrane protein, GAPDH functions in endocytosis; in the cytoplasm, i t is involved in the translational control of gene expression; in the nucleus, it functions in nuclear tRNA export, in DNA replication, and in DNA repair. The intracellular localization of GAPDH may be dependen t on the proliferative state of the cell. Recent studies identified a role for GAPDH in neuronal apoptosis. GAPDH gene expression was specif ically increased during programmed neuronal cell death. Transfection o f neuronal cells with antisense GAPDH sequences inhibited apoptosis. L astly, GAPDH may be directly involved in the cellular phenotype of hum an neurodegenerative disorders, especially those characterized at the molecular level by the expansion of CAG repeats. In this review, the c urrent status of ongoing GAPDH studies are described (with the excepti on of its unique oxidative modification by nitric oxide). Consideratio n of future directions are suggested. (C) 1997 Wiley-Liss, Inc.