Transcriptional induction of Smurf2 ubiquitin ligase by TGF-β
Transcriptional induction of Smurf2 ubiquitin ligase by TGF-β
复制标题
DOI：
10.1016/j.febslet.2005.03.069
复制
发表时间：
2005-05-09
期刊：
影响因子：
3.5
通讯作者：
Kitagawa, M
中科院分区：
文献类型：
--
作者：
Ohashi, N;Yamamoto, T;Kitagawa, M
Smad泛素化调节因子2(Smad泛素化调节因子2)是Smads的泛素连接酶，通过依赖泛素的Smad2和Smad7的降解，在转化生长因子-β(TGF-β)-Smad信号的调节中发挥关键作用。我们发现转化生长因子-β刺激S-MURF2的表达。转化生长因子-β可激活转化生长因子反应细胞系中的S-2启动子，而IL-1α、PDGF和表皮生长因子则不能。Smad7或激活素受体样激酶5抑制剂可抑制转化生长因子-β介导的SMurf2启动子的激活，但不受显性负性Smad或Smad结合元件的破坏。此外，抑制磷脂酰肌醇3激酶(PI3K)/Akt通路可抑制转化生长因子-β介导的SMurf2诱导。这些结果提示，转化生长因子-β通过Smad非依赖性途径，如PI3K/Akt途径，通过转化生长因子-β受体刺激SMurf2的表达。(C)2005年欧洲生化学会联合会。爱思唯尔出版，版权所有。
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.