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 ...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.展开更多
基金grants from the National Key Scientific Program of China(2011CB943902)the National Natural Science Foundation of China(30971679,3107126A,31271531,and 31771615)the Fundamental Research Funds for the Central Universities(090314380019).
文摘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.
