| First Author | Chae JS | Year | 2012 |
| Journal | Free Radic Biol Med | Volume | 53 |
| Issue | 12 | Pages | 2335-43 |
| PubMed ID | 23085515 | Mgi Jnum | J:193773 |
| Mgi Id | MGI:5469542 | Doi | 10.1016/j.freeradbiomed.2012.10.527 |
| Citation | Chae JS, et al. (2012) Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1. Free Radic Biol Med 53(12):2335-43 |
| abstractText | 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-alpha prevented the physical interaction between thioredoxin-1 and MST1 and promoted the homodimerization and activation of MST1. The effect of TNF-alpha 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. |
