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 ）
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）
- 生命科学－已发表论文 
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.