STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling.
STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling.
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STAT3 选择性地与 Smad3 相互作用以拮抗 TGF-β 信号传导
DOI：
10.1038/onc.2015.446
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发表时间：
2016-08-18
期刊：
影响因子：
8
通讯作者：
Feng XH
中科院分区：
文献类型：
--
作者：
Wang G;Yu Y;Sun C;Liu T;Liang T;Zhan L;Lin X;Feng XH
Smad和STAT蛋白是控制细胞生长和肿瘤发生的关键信号转导和转录因子。在这里，我们报道STAT3信号通路通过Smad3-STAT3直接相互作用减弱TGF-β诱导的应答。活化的STAT3减弱TGF-β介导的信号传导。STAT3的缺失促进TGF-β介导的转录和生理反应，包括细胞周期阻滞、细胞凋亡和上皮到间质转化。STAT3在体内和体外直接与Smad3相互作用，导致Smad3- smad4复合物形成衰减，抑制Smad3的dna结合能力。STAT3 dna结合域的n端区域负责STAT3- smad3相互作用，也是STAT3介导的TGF-β信号抑制不可或缺的区域。因此，我们的发现说明了STAT3和Smad3信号通路之间的直接串扰可能有助于肿瘤的发展和炎症。
Smad and STAT proteins are critical signal transducers and transcription factors in controlling cell growth and tumorigenesis. Here we report that the STAT3 signaling pathway attenuates TGF-β-induced responses through a direct Smad3-STAT3 interplay. Activated STAT3 blunts TGF-β-mediated signaling. Depletion of STAT3 promotes TGF-β-mediated transcriptional and physiological responses, including cell cycle arrest, apoptosis and epithelial-to-mesenchymal transition. STAT3 directly interacts with Smad3 in vivo and in vitro, resulting in attenuation of the Smad3-Smad4 complex formation and suppression of DNA-binding ability of Smad3. The N-terminal region of DNA-binding domain of STAT3 is responsible for the STAT3-Smad3 interaction and also indispensable for STAT3-mediated inhibition of TGF-β signaling. Thus, our finding illustrates a direct crosstalk between the STAT3 and Smad3 signaling pathways that may contribute to tumor development and inflammation.