Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling.

Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling.
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DOI:
10.1038/srep07596
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发表时间:
2014-12-23
期刊:
影响因子:
4.6
通讯作者:
Katagiri T
Katagiri T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tsukamoto S;Mizuta T;Fujimoto M;Ohte S;Osawa K;Miyamoto A;Yoneyama K;Murata E;Machiya A;Jimi E;Kokabu S;Katagiri T

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Smad 1、Smad 5和Smad 9(也称为Smad 8)通过骨形态发生蛋白(BMP)结合的I型受体激酶磷酸化而活化。我们通过创建组成型活性形式(SmadDVD)来研究Smad 1、Smad 5和Smad 9的作用。Smad 9DVD的转录活性低于Smad 1DVD或Smad 5DVD,尽管所有三个SmadDVD都与Smad 4结合并与靶DNA结合。Smad 9的接头区足以降低转录活性。Smad 9的表达增加了BMP信号的激活,类似于抑制性Smads(I-Smads),和Smad 9降低BMP活性。然而,与I-Smads相反,Smad 9不抑制I型受体激酶,并抑制组成型活性Smad 1DVD。Smad 9与Smad 1形成复合物并与DNA结合,但抑制靶基因的转录。综上所述,我们的研究结果表明,Smad 9是一种新型的BMP信号转录调节因子。
Smad1, Smad5 and Smad9 (also known as Smad8) are activated by phosphorylation by bone morphogenetic protein (BMP)-bound type I receptor kinases. We examined the role of Smad1, Smad5, and Smad9 by creating constitutively active forms (SmadDVD). Transcriptional activity of Smad9DVD was lower than that of Smad1DVD or Smad5DVD, even though all three SmadDVDs associated with Smad4 and bound to the target DNA. The linker region of Smad9 was sufficient to reduce transcriptional activity. Smad9 expression was increased by the activation of BMP signaling, similar to that of inhibitory Smads (I-Smads), and Smad9 reduced BMP activity. In contrast to I-Smads, however, Smad9 did not inhibit the type I receptor kinase and suppressed the constitutively active Smad1DVD. Smad9 formed complexes with Smad1 and bound to DNA but suppressed the transcription of the target gene. Taken together, our findings suggest that Smad9 is a new type of transcriptional regulator in BMP signaling.
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