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. 2010 Aug;12(8):781-90.
doi: 10.1038/ncb2082. Epub 2010 Jul 18.

Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation

Chan Gao  1 , Weipeng Cao, Lan Bao, Wei Zuo, Guoming Xie, Tiantian Cai, Wei Fu, Jian Zhang, Wei Wu, Xu Zhang, Ye-Guang Chen
Affiliations

Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation

Chan Gao et al. Nat Cell Biol. 2010 Aug.

Abstract

In eukaryotic cells, autophagy is a highly conserved self-digestion process to promote cell survival in response to nutrient starvation and other metabolic stresses. Autophagy is regulated by cell signalling such as the mTOR (mammalian target of rapamycin) pathway. However, the significance of autophagy in modulation of signal transduction is unclear. Here we show that autophagy negatively regulates Wnt signalling by promoting Dishevelled (Dvl) degradation. Von Hippel-Lindau protein-mediated ubiquitylation is critical for the binding of Dvl2 to p62, which in turn facilitates the aggregation and the LC3-mediated autophagosome recruitment of Dvl2 under starvation; the ubiquitylated Dvl2 aggregates are ultimately degraded through the autophagy-lysosome pathway. Moreover, a reverse correlation between Dvl expression and autophagy is observed in late stages of colon cancer development, indicating that autophagy may contribute to the aberrant activation of Wnt signalling in tumour formation.

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