GST Regulation of Apoptosis

Science's STKE  24 Apr 2001:
Vol. 2001, Issue 79, pp. tw8
DOI: 10.1126/stke.2001.79.tw8

Glutatione S-transferases (GSTs) are most commonly known as enzymes that conjugate reduced glutathione to a variety of substrates. However, in addition to this catalytic activity, GSTs have other nonenzymatic activities, including binding to lipophilic compounds like steroid hormones. Cho et al. report yet another property for the Mu class of GST--it appears to negatively regulate apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase that activates the c-Jun NH2-terminal kinase and the p38 signaling pathways in response to proinflammatory cytokines and to cellular stress conditions. An interaction was detected through a yeast two-hybrid screen and confirmed in vitro with purified proteins and in vivo with endogenous proteins in mouse liver tissue. Overexpression of GST inhibited ASK1 activity and ASK1-dependent cell death in stress-stimulated transfected cells. These actions did not require GST enzymatic activity. Overexpressed GST blocked ASK1 oligomerization, providing a possible mechanism of ASK1 signaling suppression.

S.-G. Cho, Y. H. Lee, H.-S. Park, K. Ryoo, K. W. Kang, J. Park, S.-J. Eom, M. J. Kim, T.-S. Chang, S.-Y. Choi, J. Shim, Y. Kim, M.-S. Dong, M.-J. Lee, S. G. Kim, H. Ichijo, E.-J. Choi, Glutathione S-transferase Mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J. Biol. Chem. 276, 12749-12755 (2001). [Abstract] [Full Text]