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Updated: Jan 27, 2026

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
Published on: December 5, 2019
E3 ligase Herc4 regulates Hedgehog signalling through promoting Smoothened degradation
Weirong Jiang1, Xia Yao1, Zhaoliang Shan1
1State 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:
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.
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