Smad3 is acetylated by p300/CBP to regulate its transactivation activity
Smad3 is acetylated by p300/CBP to regulate its transactivation activity
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DOI：
10.1038/sj.onc.1209826
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发表时间：
2007-01-25
期刊：
影响因子：
8
通讯作者：
Hayashi, H.
中科院分区：
文献类型：
--
作者：
Inoue, Y.;Itoh, Y.;Hayashi, H.
Smad蛋白对于转化生长因子-P（TGF-β）的细胞内信号传导至关重要。在它们的受体诱导的激活后，Smad蛋白被磷酸化并易位到细胞核以激活一组选定的靶基因的转录。在这里，我们表明，共激活剂p300/CBP结合和乙酰化的Smad 3以及Smad 2在体内，和乙酰化刺激TGF-β。p300/CBP对Smad 3的一个主要乙酰化位点是MH 2结构域（Smad 3C）中的Lys-378，已知其对转录活性的调节至关重要。在荧光素酶测定中，用Arg替换Lys-378降低了GAL 4-Smad 3C的转录活性。此外，p300/CBP增强了GAL 4-Smad 3C的转录活性，但不增强乙酰化抗性GAL 4-Smad 3C（K378 R）突变体的转录活性。这些结果表明，Smad 3的乙酰化p300/CBP正向调节其转录活性。
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.