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Modulation of lysine acetylation‐stimulated repressive activity by Erk2‐mediated phosphorylation of RIP140 in adipocyte differentiation
Author(s) -
Ho PingChih,
Gupta Pawan,
Tsui YaoChen,
Ha Sung gil,
Huq MD Mastaqul,
Wei LiNa
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.585.3
Subject(s) - acetylation , phosphorylation , lysine , signal transduction , threonine , chemistry , microbiology and biotechnology , mutant , kinase , biochemistry , serine , biology , gene , amino acid
Receptor‐interacting protein 140 is a co‐regulator for transcription factors. Previous studies showed that either phosphorylation or lysine acetylation of RIP140 directly enhanced its trans‐repressive activity. Here, we identified p300 as a specific lysine acetyltransferase, and ERK2 as a specific kinase for threonine phosphorylation, of RIP140 in vivo. We further determined two specific acetylated lysine residues (Lys158/Lys287) that were critical for its gene repressive activity. We then delineated signal transduction from Erk2‐mediated phosphorylation of RIP140 that enhanced its recruiting p300 for subsequent lysine acetylation, and demonstrated the kinetics of activation of this signal transduction pathway in differentiating adipocytes. The physiological significance of this cell signal transduction pathway was illustrated in rescuing experiments where the defect in fat accumulation of RIP140‐null cultures was rescued by re‐expressing the wild type RIP140 or its phospho‐mimetic mutant, but not its acetylation deficient mutant. These results demonstrate ERK2‐meidated threonine phosphorylation, followed by p300 recruitment for lysine acetylation, which ultimately enhances the gene‐repressive activity of RIP140 and its role in fat accumulation in differentiated adipoctyes. This work was supported by DK 54733, DK 60521, K02‐DA13926 and DA11190 to L.‐N. Wei.