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

Oncogene. 2007 Jan 25;26(4):500-8. doi: 10.1038/sj.onc.1209826.

Y Inoue ¹, Y Itoh, K Abe, T Okamoto, H Daitoku, A Fukamizu, K Onozaki, H Hayashi

Affiliations

Affiliation

1 Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.

PMID: 16862174 DOI: 10.1038/sj.onc.1209826

Abstract

Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (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.

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