Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1

Ji Soo Chae, Sang Gil Hwang, Dae Sik Lim, Eui Ju Choi

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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 languageEnglish
Pages (from-to)2335-2343
Number of pages9
JournalFree Radical Biology and Medicine
Volume53
Issue number12
DOIs
Publication statusPublished - 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)

Fingerprint

Dive into the research topics of 'Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1'. Together they form a unique fingerprint.

Cite this