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

被引：0
作者：
Y Inoue
Y Itoh
K Abe
T Okamoto
H Daitoku
A Fukamizu
K Onozaki
H Hayashi
机构：
[1] Graduate School of Pharmaceutical Sciences,Department of Molecular Health Sciences
[2] Nagoya City University,Department of Molecular and Cellular Biology
[3] Nagoya City University Graduate School of Medical Sciences,Department of Biochemistry 1
[4] Center for Tsukuba Advanced Research Alliance,undefined
[5] Institute of Applied Biochemistry,undefined
[6] University of Tsukuba,undefined
[7] Research Institute,undefined
[8] National Cancer Center,undefined
[9] Hamamatsu University School of Medicine,undefined
来源：
Oncogene | 2007年 / 26卷
关键词：
acetylation; CBP; p300; Smad2; Smad3; TGF-;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Smad proteins are crucial for the intracellular signaling of transforming growth factor-β (TGF-β). 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-β. 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.
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页码：500 / 508
页数：8
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