Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses
Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses
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DOI：
10.1016/j.bbagrm.2014.12.008
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发表时间：
2015-03-01
影响因子：
4.7
通讯作者：
Xu, Zhi-Qing David
中科院分区：
文献类型：
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作者：
Yang, Yutao;Cui, Jiajun;Xu, Zhi-Qing David
Pokemon是一种重要的原癌蛋白，是一种属于POK （POZ和Kruppel）家族的转录抑制因子。Smad4是tgf - β通路的关键组分，在tgf - β诱导的转录反应中起重要作用。在这项研究中，我们发现Pokemon在体内和体外都可以直接与Smad4相互作用。过度表达Pokemon会降低tgf - β诱导的转录活动，而敲低Pokemon则会增加这些活动。有趣的是，Pokemon并不影响Smad2/3的激活、Smads复合物的形成或Smad4的DNA结合活性。tgf - β 1处理增加了Pokemon与Smad4之间的相互作用，也增强了Pokemon向Smad4- dna复合体的招募。此外，我们还发现Pokemon将HDAC1招募到Smad4复合体中，但减少了Smad4与p300/CBP之间的相互作用。综上所述，这些数据表明Pokemon是Smad4的新伙伴，在TGF-beta通路中起负作用。(C) 2014年Elsevier B.V.出版
Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Kruppel) family. Smad4, a key component of TGF-beta pathway, plays an essential role in TGF-beta-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-beta-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-beta 1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-beta pathway. (C) 2014 Published by Elsevier B.V.