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SP600125 negatively regulates the mammalian target of rapamycin via ATF4‐induced Redd1 expression
Author(s) -
Jin Hyeon-Ok,
Seo Sung-Keum,
Woo Sang-Hyeok,
Kim Eun-Sung,
Lee Hyung-Chahn,
Yoo Doo-Hyun,
Choe Tae-Boo,
Hong Seok-Il,
Kim Jong-Il,
Park In-Chul
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.035
Subject(s) - phosphorylation , gene knockdown , p70 s6 kinase 1 , atf4 , pi3k/akt/mtor pathway , downregulation and upregulation , chemistry , kinase , microbiology and biotechnology , cancer research , signal transduction , protein kinase b , biology , gene , biochemistry
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.