Smad3 is acetylated by p300 CBP to regulate its transactivation activity

• Published in: Oncogene Vol. 26; no. 4; pp. 500 - 508
• Main Authors: INOUE, Y, ITOH, Y, ABE, K, OKAMOTO, T, DAITOKU, H, FUKAMIZU, A, ONOZAKI, K, HAYASHI, H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 25-01-2007; Nature Publishing Group
• Subjects: Acetylation; Acetyltransferases - metabolism; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetic regulation; Genetic transcription; Genetics; Humans; Molecular and cellular biology; Oncology; p300-CBP Transcription Factors - metabolism; Phosphorylation; Physiological aspects; Protein-Serine-Threonine Kinases - metabolism; Proteins; Receptors, Transforming Growth Factor beta; Signal transduction; Smad2 Protein - metabolism; Smad3 Protein - metabolism; Transcriptional Activation; Transfection; Transforming Growth Factor beta - physiology; Transforming growth factors; Japan; CBP; p300; Smad2; Regulation(control); Smad protein; Smad3; Acetylation; Carcinogenesis; TGF-fi; Cell signaling
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1209826

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.