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 |
|---|---|
| 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 |
Fingerprint
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 journal › Article
}
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 - Thioredoxin-1
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=84870294580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870294580&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2012.10.527
DO - 10.1016/j.freeradbiomed.2012.10.527
M3 - Article
VL - 53
SP - 2335
EP - 2343
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 12
ER -