TY - JOUR
T1 - Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1
AU - Chae, Ji Soo
AU - Gil Hwang, Sang
AU - Lim, Dae Sik
AU - Choi, Eui Ju
PY - 2012/12/15
Y1 - 2012/12/15
N2 - 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.
AB - 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.
KW - Free radicals
KW - MST1
KW - Reactive oxygen species
KW - TNF-α
KW - Thioredoxin-1
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U2 - 10.1016/j.freeradbiomed.2012.10.527
DO - 10.1016/j.freeradbiomed.2012.10.527
M3 - Article
C2 - 23085515
AN - SCOPUS:84870294580
VL - 53
SP - 2335
EP - 2343
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 12
ER -