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Sin1 binds to both ATF‐2 and p38 and enhances ATF‐2‐dependent transcription in an SAPK signaling pathway
Author(s) -
Makino Chieko,
Sano Yuji,
Shinagawa Toshie,
Millar Jonathan B. A.,
Ishii Shunsuke
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.01016.x
Subject(s) - p38 mitogen activated protein kinases , activating transcription factor 2 , microbiology and biotechnology , transcription factor , phosphorylation , biology , signal transduction , gene knockdown , ask1 , protein kinase a , gene expression , apoptosis , mitogen activated protein kinase kinase , gene , promoter , biochemistry
Yeast Sin1 binds to the Sty1 kinase, a member of the stress‐activated kinases (SAPKs), and is required for stress‐induced phosphorylation and activation of the transcription factor Atf1, a homolog of the vertebrate‐activating transcription factor‐2 (ATF‐2). Here we report that mammalian Sin1 plays an important role in the SAPK signaling pathway by binding to both ATF‐2 and p38. In response to stress, ATF‐2, a member of the ATF/cAMP response element‐binding protein family, is phosphorylated by p38/Jun NH 2 ‐terminal protein kinase and activates the transcription of apoptosis‐related genes. In contrast, in response to serum stimulation, ATF‐2 is phosphorylated via the Ras effector pathway and leads to the induction of growth‐related genes. We found that Sin1 binds directly to both ATF‐2 and p38. Sin1 over‐expression enhanced osmotic stress‐induced phosphorylation of ATF‐2 and ATF‐2‐mediated transcription, whereas knockdown of Sin1 expression by siRNA suppressed these responses. Moreover, a reduction in Sin1 expression suppressed osmotic stress‐induced apoptosis and the expression of Gadd45β, one of the ATF‐2 target genes that is correlated with apoptosis. Decreased Sin1 expression, however, did not affect the serum stimulation‐induced phosphorylation of ATF‐2. Sin1 may contribute to ATF‐2 signaling specificity by acting as a nuclear scaffold.