Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Machiya A, Jimi E, Kokabu S, Katagiri T
Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
School of Medical Technology and Health, Faculty of Health and Medical Care, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
Sci Rep. 2014 Dec 23;4:7596. doi: 10.1038/srep07596.
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 (Smad(DVD)). Transcriptional activity of Smad9(DVD) was lower than that of Smad1(DVD) or Smad5(DVD), even though all three Smad(DVD)s 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 Smad1(DVD). 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.
Smad1、Smad5和Smad9（也称为Smad8）通过与骨形态发生蛋白（BMP）结合的I型受体激酶磷酸化而被激活。我们通过创建组成型激活形式（Smad(DVD)）来研究Smad1、Smad5和Smad9的作用。尽管所有三种Smad(DVD)都与Smad4结合并与靶DNA结合，但Smad9(DVD)的转录活性低于Smad1(DVD)或Smad5(DVD)。Smad9的连接区足以降低转录活性。与抑制性Smad（I-Smad）类似，BMP信号激活会增加Smad9的表达，并且Smad9会降低BMP活性。然而，与I-Smad不同的是，Smad9不抑制I型受体激酶，而是抑制组成型激活的Smad1(DVD)。Smad9与Smad1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Smad9是BMP信号通路中的一种新型转录调节因子。
