E1A Inhibits Transforming Growth Factor-β Signaling through Binding to Smad Proteins

Smads form a recently identified family of proteins that mediate intracellular signaling of the transforming growth factor (TGF)-β superfamily. Smads bind to DNA and act as transcriptional regulators. Smads interact with a variety of transcription factors, and the interaction is likely to determine...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-10, Vol.274 (40), p.28716
Main Authors: Ayako Nishihara, Jun-ichi Hanai, Takeshi Imamura, Kohei Miyazono, Masahiro Kawabata
Format: Article
Language:English
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Summary:Smads form a recently identified family of proteins that mediate intracellular signaling of the transforming growth factor (TGF)-β superfamily. Smads bind to DNA and act as transcriptional regulators. Smads interact with a variety of transcription factors, and the interaction is likely to determine the target specificity of gene induction. Smads also associate with transcriptional coactivators such as p300 and CBP. E1A, an adenoviral oncoprotein, inhibits TGF-β-induced transactivation, and the ability of E1A to bind p300/CBP is required for the inhibition. Here we determined the Smad interaction domain (SID) in p300 and found that two adjacent regions are required for the interaction. One of the regions is the C/H3 domain conserved between p300 and CBP, and the other is a nonconserved region. p300 mutants containing SID inhibit transactivation by TGF-β in a dose-dependent manner. E1A inhibits the interaction of Smad3 with a p300 mutant that contains SID but lacks the E1A binding domain. We found that E1A interacts specifically with receptor-regulated Smads, suggesting a novel mechanism whereby E1A antagonizes TGF-β signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.40.28716