Affiliation:
1. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, China
Abstract
Abstract
Hedgehog (Hh) signalling plays conserved roles in controlling embryonic development; its dysregulation causes many diseases including cancers. The G protein-coupled receptor Smoothened (Smo) is the key signal transducer of the Hh pathway, whose posttranslational regulation has been shown to be critical for its accumulation and activation. Ubiquitination has been reported an essential posttranslational regulation of Smo. Here, we identify a novel E3 ligase of Smo, Herc4, which binds to Smo, and regulates Hh signalling by controlling Smo ubiquitination and degradation. Interestingly, our data suggest that Herc4-mediated Smo degradation is regulated by Hh in PKA-primed phosphorylation-dependent and independent manners.
Funder
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
National Key Scientific Program of China
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Genetics,Molecular Biology,General Medicine
Cited by
23 articles.
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