Mutant Huntingtin: Nuclear translocation and cytotoxicity mediated by GAPDH. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. I., Xu, H., Igarashi, S., Fujimuro, M., Agrawal, N., Taya, Y., Hayward, S. Thus, novel cytoprotective therapies may emerge from agents that prevent GAPDH-Siah binding.īae, B. The neuroprotective actions of the monoamine oxidase inhibitor R-(-)-deprenyl (deprenyl) reflect blockade of GAPDH-Siah binding. The cytotoxicity of mutant Huntingtin (mHtt) requires nuclear translocation which appears to be mediated via a ternary complex of GAPDH-Siah-mHtt. In the nucleus, GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected target proteins and affect apoptosis.ģ. The S-nitrosylation abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah, an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. A wide range of apoptotic stimuli activate NO formation, which S-nitrosylates GAPDH. This paper reviews the GAPDH cell death cascade and discusses its clinical relevance.Ģ. Recent studies indicate that it is a major intracellular messenger mediating apoptotic cell death. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly unrelated functions.
0 kommentar(er)
