Back to Search
Start Over
Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2001 Apr 20; Vol. 276 (16), pp. 12749-55. Date of Electronic Publication: 2001 Jan 18. - Publication Year :
- 2001
-
Abstract
- Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that can activate the c-Jun N-terminal kinase and the p38 signaling pathways. It plays a critical role in cytokine- and stress-induced apoptosis. To further characterize the mechanism of the regulation of the ASK1 signal, we searched for ASK1-interacting proteins employing the yeast two-hybrid method. The yeast two-hybrid assay indicated that mouse glutathione S-transferase Mu 1-1 (mGSTM1-1), an enzyme involved in the metabolism of drugs and xenobiotics, interacted with ASK1. We subsequently confirmed that mGSTM1-1 physically associated with ASK1 both in vivo and in vitro. The in vitro binding assay indicated that the C-terminal portion of mGSTM1-1 and the N-terminal region of ASK1 were crucial for binding one another. Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization. The ASK1 inhibition by mGSTM1-1 occurred independently of the glutathione-conjugating activity of mGSTM1-1. Moreover, mGSTM1-1 repressed ASK1-dependent apoptotic cell death. Taken together, our findings suggest that mGSTM1-1 functions as an endogenous inhibitor of ASK1. This highlights a novel function for mGSTM1-1 insofar as mGSTM1-1 may modulate stress-mediated signals by repressing ASK1, and this activity occurs independently of its well-known catalytic activity in intracellular glutathione metabolism.
- Subjects :
- Animals
Binding Sites
Cloning, Molecular
Isoenzymes metabolism
JNK Mitogen-Activated Protein Kinases
Liver enzymology
Luciferases genetics
MAP Kinase Kinase Kinase 5
MAP Kinase Kinase Kinases chemistry
Mice
Mitogen-Activated Protein Kinases metabolism
Proto-Oncogene Proteins c-jun metabolism
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Saccharomyces cerevisiae
Transcription, Genetic
Glutathione Transferase metabolism
MAP Kinase Kinase Kinases metabolism
MAP Kinase Signaling System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 276
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11278289
- Full Text :
- https://doi.org/10.1074/jbc.M005561200