Transcriptional induction of Smurf2 ubiquitin ligase by TGF-β

被引：74

作者：

Ohashi, N

Yamamoto, T

Uchida, C

Togawa, A

Fukasawa, H

Fujigaki, Y

Suzuki, S

Kitagawa, K

Hattori, T

Oda, T

Hayashi, H

Hishida, A

Kitagawa, M

机构：

[1] Hamamatsu Univ Sch Med, Dept Med 1, Hamamatsu, Shizuoka 4313192, Japan

[2] Hamamatsu Univ Sch Med, Dept Biochem 1, Hamamatsu, Shizuoka 4313192, Japan

[3] Nagoya City Univ, Grad Sch Pharmaceut Sci, Dept Mol Hlth Sci, Nagoya, Aichi, Japan

来源：

FEBS LETTERS | 2005年 / 579卷 / 12期

关键词：

TGF-beta; Smurf22; gene expression; signal transduction; ubiquitin ligase;

D O I：

10.1016/j.febslet.2005.03.069

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1 alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：2557 / 2563

页数：7

共 34 条

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