Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia | |
Liu, Wei(Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China ) ; Rui, Hongliang(Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China ) ; Wang, Jifeng ; Lin, Shuyong ; Lin SY(林舒勇) ; He, Ying ; Chen, Mingliang ; Li, Qinxi ; Ye, Zhiyun ; Ye ZY(叶志云) ; Zhang, Suping ; Chan, Siu Chiu(Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China ) ; Chen, Ye-Guang(State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University) ; Han, Jiahuai ; Han JH(韩家淮) ; Lin, Sheng-Cai ; Lin SC(林圣彩) | |
2006 | |
关键词 | Arkadia Axin Smad7 TGF-beta ubiquitination |
英文摘要 | TGF-beta signaling involves a wide array of signaling molecules and multiple controlling events. Scaffold proteins create a functional proximity of signaling molecules and control the specificity of signal transduction. While many components involved in the TGF-beta pathway have been elucidated, little is known about how those components are coordinated by scaffold proteins. Here, we show that Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia. Axin depends on Arkadia to facilitate TGF-beta signaling, as their small interfering RNAs reciprocally abolished the stimulatory effect on TGF-beta signaling. Specific knockdown of Axin or Arkadia revealed that Axin and Arkadia cooperate with each other in promoting Smad7 ubiquitination. Pulse-chase experiments further illustrated that Axin significantly decreased the half-life of Smad7. Axin also induces nuclear export of Smad7. Interestingly, Axin associates with Arkadia and Smad7 independently of TGF-beta signal, in contrast to its transient association with inactive Smad3. However, coexpression of Wnt-1 reduced Smad7 ubiquitination by down-regulating Axin levels, underscoring the importance of Axin as an intrinsic regulator in TGF-beta signaling. |
语种 | 英语 |
出版者 | NATURE PUBLISHING GROUP |
内容类型 | 期刊论文 |
源URL | [http://dx.doi.org/doi:10.1038/sj.emboj.7601057] ![]() |
专题 | 生命科学-已发表论文 |
推荐引用方式 GB/T 7714 | Liu, Wei,Rui, Hongliang,Wang, Jifeng,et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia[J],2006. |
APA | Liu, Wei.,Rui, Hongliang.,Wang, Jifeng.,Lin, Shuyong.,林舒勇.,...&林圣彩.(2006).Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia.. |
MLA | Liu, Wei,et al."Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia".(2006). |
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