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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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