E3 ligase Herc4 regulates Hedgehog signalling through promoting Smoothened degradation
E3 ligase Herc4 regulates Hedgehog signalling through promoting Smoothened degradation
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E3 连接酶 Herc4 通过促进平滑降解来调节 Hedgehog 信号传导
DOI：
10.1093/jmcb/mjz024
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发表时间：
2019-09-01
影响因子：
5.5
通讯作者：
Zhang, Qing
中科院分区：
文献类型：
--
作者：
Jiang, Weirong;Yao, Xia;Zhang, Qing
摘要Hedgehog（Hh）信号在胚胎发育中起着保守的作用，其失调导致包括癌症在内的多种疾病。G蛋白偶联受体Smoothened（Smo）是Hh信号通路的关键信号转导子，其翻译后调节对Hh的积累和激活至关重要。泛素化被认为是Smo的重要翻译后调节。在这里，我们确定了一种新的E3连接酶Smo，Herc4，它结合到Smo，并通过控制Smo泛素化和降解调节Hh信号。有趣的是，我们的数据表明，Herc4介导的Smo降解是由Hh在PKA引发的磷酸化依赖和独立的方式。
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.