The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation
The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation
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DOI：
10.1101/gad.12.14.2153
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发表时间：
1998-07-15
影响因子：
10.5
通讯作者：
Derynck, R
中科院分区：
文献类型：
--
作者：
Feng, XH;Zhang, Y;Derynck, R
smad调节特定基因的转录以响应tgf - β受体的激活，尽管smad介导的转录机制尚不清楚。我们证明tgf - β诱导的Smad3使用肿瘤抑制因子Smad4/DPC4和CBP/p300作为转录共激活因子，它们在响应tgf - β时与Smad3相关。CBP与Smad3的关联定位于Smad3的羧基端，这是转录激活所必需的，也是CBP中一个确定的片段。此外，CBP/p300以Smad4/ dpc4依赖的方式刺激tgf - β和smad诱导的转录。表达干扰CBP功能的E1A可抑制Smad3反式激活和tgf - β诱导的转录。Smad4和CBP/p300与Smad3的共激活子功能和物理相互作用为诱导基因表达响应tgf - β提供了一个模型。
Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate with Smad3 in response to TGF-beta. 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-beta- and Smad-induced transcription in a Smad4/DPC4-dependent fashion. Smad3 transactivation and TGF-beta-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-beta.