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 journalArticle

27 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

Fingerprint

Thioredoxins
Oxidative stress
Oxidative Stress
Phosphotransferases
Chemical activation
Switches
Acetylcysteine
Protein-Serine-Threonine Kinases
Reducing Agents
Cell death
Cell Communication
Cysteine
Cell Death
Cells

Keywords

  • Free radicals
  • MST1
  • Reactive oxygen species
  • Thioredoxin-1
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1. / Chae, Ji Soo; Gil Hwang, Sang; Lim, Dae Sik; Choi, Eui Ju.

In: Free Radical Biology and Medicine, Vol. 53, No. 12, 15.12.2012, p. 2335-2343.

Research output: Contribution to journalArticle

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