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

被引：92

作者：

Tsukamoto, S. ^{[1
]}

Mizuta, T. ^{[1
]}

Fujimoto, M. ^{[1
]}

Ohte, S. ^{[1
]}

Osawa, K. ^{[1
]}

Miyamoto, A. ^{[1
]}

Yoneyama, K. ^{[1
]}

Murata, E. ^{[2
]}

Machiya, A. ^{[1
]}

Jimi, E. ^{[3
]}

Kokabu, S. ^{[1
,4
]}

Katagiri, T. ^{[1
]}

机构：

[1] Saitama Med Univ, Div Pathophysiol, Res Ctr Genom Med, Saitama 3501241, Japan

[2] Saitama Med Univ, Sch Med Technol & Hlth, Fac Hlth & Med Care, Saitama 3501241, Japan

[3] Kyushu Dent Univ, Div Mol Signaling & Biochem, Dept Hlth Promot, Kokurakita Ku, Kitakyushu, Fukuoka 8038580, Japan

[4] Saitama Med Univ, Dept Oral & Maxillofacial Surg, Fac Med, Moroyama, Saitama 3500495, Japan

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

关键词：

TGF-BETA RECEPTOR; I RECEPTORS; BMP; IDENTIFICATION; OSTEOBLAST; ID1; PHOSPHATASES; INHIBITION; ANTAGONIST; ACTIVATION;

D O I：

10.1038/srep07596

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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