肿瘤抑制因子Smad4/DPC4和转录衔接蛋白CBP/p300是转化生长因子β（TGF-β）诱导的转录激活过程中Smad3的共激活因子。
The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation.
作者信息
Feng X H, Zhang Y, Wu R Y, Derynck R
机构信息
Departments of Growth and Development and Anatomy, and Programs in Cell Biology and Developmental Biology, University of California, San Francisco, California 94143-0640 USA.
出版信息
Genes Dev. 1998 Jul 15;12(14):2153-63. doi: 10.1101/gad.12.14.2153.
Abstract
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.
摘要
Smads可响应TGF-β受体激活来调节特定基因的转录，尽管Smad介导的转录机制尚未完全明确。我们证明，TGF-β诱导的Smad3利用肿瘤抑制因子Smad4/DPC4和CBP/p300作为转录共激活因子，它们在TGF-β作用下与Smad3结合。CBP与Smad3的结合定位于Smad3的羧基末端，这是转录激活所必需的，且位于CBP的一个特定区域。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以及CBP/p300与Smad3的共激活因子功能和物理相互作用为响应TGF-β诱导基因表达提供了一个模型。
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