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Axin is a scaffold protein in TGF-β signaling that promotes degradation of Smad7 by Arkadia
被引:144
作者:
Liu, Wei
Rui, Hongliang
Wang, Jifeng
Lin, Shuyong
He, Ying
Chen, Mingliang
Li, Qinxi
Ye, Zhiyun
Zhang, Suping
Chan, Siu Chiu
Chen, Ye-Guang
Han, Jiahuai
Lin, Sheng-Cai
[1
]
机构:
[1] Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China
[2] Xiamen Univ, Key Lab Cell Biol & Tumor Cell Engn, Sch Life Sci, Minist Educ, Fujian, Peoples R China
[3] Tsing Hua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Dept Biol Sci & Biotechnol, Beijing 100084, Peoples R China
[4] Scripps Res Inst, Dept Immunol, La Jolla, CA USA
关键词:
Arkadia;
Axin;
Smad7;
TGF-beta;
ubiquitination;
D O I:
10.1038/sj.emboj.7601057
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
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.
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页码:1646 / 1658
页数:13
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