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Publication : SP600125 negatively regulates the mammalian target of rapamycin via ATF4-induced Redd1 expression.

First Author  Jin HO Year  2009
Journal  FEBS Lett Volume  583
Issue  1 Pages  123-7
PubMed ID  19059405 Mgi Jnum  J:142693
Mgi Id  MGI:3821961 Doi  10.1016/j.febslet.2008.11.035
Citation  Jin HO, et al. (2009) SP600125 negatively regulates the mammalian target of rapamycin via ATF4-induced Redd1 expression. FEBS Lett 583(1):123-127
abstractText  SP600125 (SAPK Inhibitor II) is reported to function as a reversible ATP competitive inhibitor of c-Jun N-terminal kinase (JNK). In the present study, we show that SP600125 induces a dose-dependent decrease in mTOR activity, as assessed by reduced phosphorylation of the downstream targets S6K1 and S6, and a significant increase in the expression of Redd1. Knockdown of Redd1 expression by siRNA resulted in a recovery of decreased S6 phosphorylation by SP600125. Overexpression of ATF4 upregulated the expression of Redd1, while suppression of ATF4 expression by siRNA enhanced the level of S6 phosphorylation by downregulating the SP600125-induced increase in Redd1 expression. Together, these results indicate that SP600125 inhibits mTOR activity via an ATF4-induced increase in Redd1 expression.
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