Smad3 is acetylated by p300/CBP to regulate its transactivation activity

被引：125

作者：

Inoue, Y.

Itoh, Y.

Abe, K.

Okamoto, T.

Daitoku, H.

Fukamizu, A.

Onozaki, K.

Hayashi, H.

机构：

[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Dept Mol Hlth Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan

[2] Nagoya City Univ, Grad Sch Med Sci, Dept Mol & Cellular Biol, Mizuho Ku, Nagoya, Aichi 4678603, Japan

[3] Univ Tsukuba, Inst Appl Biochem, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 305, Japan

来源：

ONCOGENE | 2007年 / 26卷 / 04期

基金：

日本学术振兴会;

关键词：

acetylation; CBP; p300; Smad2; Smad3; TGF-beta;

D O I：

10.1038/sj.onc.1209826

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Smad proteins are crucial for the intracellular signaling of transforming growth factor-P (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta. A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity. Replacement of Lys-378 with Arg decreased the transcriptional activity of GAL4-Smad3C in a luciferase assay. Moreover, p300/CBP potentiated the transcriptional activity of GAL4-Smad3C, but not the acetylation-resistant GAL4-Smad3C(K378R) mutant. These results suggest that acetylation of Smad3 by p300/CBP regulates positively its transcriptional activity.

引用

页码：500 / 508

页数：9

共 34 条

[1] T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling [J].