TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300
TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300
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DOI：
10.1101/gad.12.14.2114
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发表时间：
1998-07-15
影响因子：
10.5
通讯作者：
Hunter, T
中科院分区：
文献类型：
--
作者：
Janknecht, R;Wells, NJ;Hunter, T
TGE-β和激活素诱导Smad2和Smad3的磷酸化和激活，但这些蛋白如何刺激基因转录却知之甚少。我们报道，Smad3的转化生长因子-β受体的磷酸化促进了它与类似的辅活化子CEP和p300的相互作用，而CBP/p300与非磷酸化的TED Smad3或其寡聚伙伴Smad4的结合受到Smad-分子内相互作用的负调控。此外，p300和TGP-β受体磷酸化的Smad3协同增强转录激活。因此，CBP/p300是激活素/转化生长因子-β信号通路的重要组成部分，可能介导Smad2和Smad4的抗肿瘤作用。
TGE-beta and activin induce the phosphorylation and activation of Smad2 and Smad3, but how these proteins stimulate gene transcription is poorly understood. We report that TGF-beta receptor phosphorylation of Smad3 promotes its interaction with, the paralogous coactivators CEP and p300, whereas CBP/p300 binding to non-phosphorylated ted Smad3 or its' oligomerization partner Smad4 is negatively regulated by Smad-intramolecular interactions. Furthermore, p300 and TGP-beta receptor-phosphorylated Smad3 synergistically augment transcriptional activation. Thus, CBP/p300 are important components of activin/TGF-beta signaling and may mediate the antioncogenic functions of Smad2 and Smad4.