Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.
Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.
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通过泛素化和去泛素化调节 Hedgehog 信号转导
DOI：
10.3390/ijms222413338
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发表时间：
2021-12-11
影响因子：
5.6
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Zhang Q;Jiang J
Hedgehog (Hh) 分泌蛋白家族控制着从昆虫到哺乳动物等物种的胚胎发育和成体组织稳态。 Hh 通路活性的失调与多种人类疾病有关，包括先天性疾病和癌症。 Hh 通过保守的信号通路发挥其生物学影响。 Hh 与其受体 Patched (Ptc)（一种十二跨度跨膜蛋白）的结合导致非典型 GPCR 家族蛋白和 Hh 信号转导器 Smoothened (Smo) 的激活，然后向下游发出信号以激活潜在的转录因子 Cubitus Interruptus (Ci)/Gli 家族。 Hh 信号转导在通路的多个步骤中受到泛素化和去泛素化的调节，包括 Ptc、Smo 和 Ci/Gli 蛋白的调节。在这里，我们回顾了泛素化和去泛素化对单个 Hh 通路组件功能的影响，涉及的 E3 泛素连接酶和去泛素化酶，泛素化和去泛素化是如何调节的，以及从果蝇到哺乳动物，其潜在机制是否保守。
The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis in species ranging from insects to mammals. Deregulation of Hh pathway activity has been implicated in a wide range of human disorders, including congenital diseases and cancer. Hh exerts its biological influence through a conserved signaling pathway. Binding of Hh to its receptor Patched (Ptc), a twelve-span transmembrane protein, leads to activation of an atypical GPCR family protein and Hh signal transducer Smoothened (Smo), which then signals downstream to activate the latent Cubitus interruptus (Ci)/Gli family of transcription factors. Hh signal transduction is regulated by ubiquitination and deubiquitination at multiple steps along the pathway including regulation of Ptc, Smo and Ci/Gli proteins. Here we review the effect of ubiquitination and deubiquitination on the function of individual Hh pathway components, the E3 ubiquitin ligases and deubiquitinases involved, how ubiquitination and deubiquitination are regulated, and whether the underlying mechanisms are conserved from Drosophila to mammals.
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