Abstract
The mammalian STE20-like kinase-1 (MST1), a multifunctional serine-threonine kinase in mammalian cells, has been recently implicated in the mediation of oxidative stress-induced signaling processes that lead to cell death. However, the molecular mechanism by which oxidative stress induces the stimulation of MST1 remains unclear. In this study, we found that thioredoxin-1 was physically associated with MST1 in intact cells and that this interaction was abolished by H2O2. Thioredoxin-1, by binding to the SARAH domain of MST1, inhibited the homodimerization and autophosphorylation of MST1, thereby preventing its activation. Furthermore, TNF-α prevented the physical interaction between thioredoxin-1 and MST1 and promoted the homodimerization and activation of MST1. The effect of TNF-α on MST1 activation was reversed by the reducing agent N-acetyl-l-cysteine. Taken together, our results suggest that thioredoxin-1 functions as a molecular switch to turn off the oxidative stress-induced activation of MST1.
Original language | English |
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Pages (from-to) | 2335-2343 |
Number of pages | 9 |
Journal | Free Radical Biology and Medicine |
Volume | 53 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2012 Dec 15 |
Bibliographical note
Funding Information:This work was supported by a grant from the Seoul R&BD Program ( ST100079 ) and by an NRF grant ( 2006–0093855, 2011–0030141 ) funded by the Ministry of Education, Science & Technology of the Korea (E.-J.C.) .
Keywords
- Free radicals
- MST1
- Reactive oxygen species
- TNF-α
- Thioredoxin-1
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)