Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.
Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.
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DOI：
10.1038/onc.2016.204
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发表时间：
2017-01-19
期刊：
影响因子：
8
通讯作者：
Feng XH
中科院分区：
文献类型：
--
作者：
Liu T;Zhao M;Liu J;He Z;Zhang Y;You H;Huang J;Lin X;Feng XH
Smad蛋白是哺乳动物细胞中典型转化生长因子-β（TGF-β）信号通路的中心介质。我们在这里报告，含溴结构域蛋白7（BRD 7）作为一种新的转录辅激活因子Smads在TGF-β信号转导。BRD 7通过其N端Smad结合结构域与Smad 3/4形成TGF-β诱导型复合物。BRD 7同时结合乙酰化组蛋白以促进Smad-染色质缔合，并与组蛋白乙酰转移酶p300缔合以增强Smad转录活性。BRD 7的异位表达，而不是其Smad结合缺陷的突变体，增强TGF-β转录、肿瘤抑制和上皮-间充质转化（EMT）反应。相反，BRD 7的耗竭抑制TGF-β应答。因此，我们的研究为BRD 7在微调TGF-β生理反应中的新功能提供了令人信服的证据。
Smad proteins are central mediators in the canonical transforming growth factor-β (TGF-β) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-β signaling. BRD7 forms a TGF-β inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-β transcriptional, tumor suppressing and epithelial-mesenchymal transition (EMT) responses. Conversely, depletion of BRD7 inhibits TGF-β responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-β physiological responses.