Author:
Feng Xin-Hua,Zhang Ying,Wu Rui-Yun,Derynck Rik
Abstract
Smads regulate transcription of defined genes in response to TGF-β receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-β-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate with Smad3 in response to TGF-β. The association of CBP with Smad3 was localized to the carboxyl terminus of Smad3, which is required for transcriptional activation, and a defined segment in CBP. Furthermore, CBP/p300 stimulated both TGF-β- and Smad-induced transcription in a Smad4/DPC4-dependent fashion. Smad3 transactivation and TGF-β-induced transcription were inhibited by expressing E1A, which interferes with CBP functions. The coactivator functions and physical interactions of Smad4 and CBP/p300 with Smad3 allow a model for the induction of gene expression in response to TGF-β.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
463 articles.
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