Targeting E3 Ubiquitin Ligases and Deubiquitinases in Ciliopathy and Cancer.

Targeting E3 Ubiquitin Ligases and Deubiquitinases in Ciliopathy and Cancer.
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在纤毛病和癌症中靶向E3泛素连接酶和去泛素化酶。

DOI:
10.3390/ijms21175962
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发表时间:
2020-08-19
影响因子:
5.6
通讯作者:
Nishimura Y
Nishimura Y
中科院分区:
生物学2区
文献类型:
--
作者:
Shiromizu T;Yuge M;Kasahara K;Yamakawa D;Matsui T;Bessho Y;Inagaki M;Nishimura Y

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纤毛是存在于许多脊椎动物细胞中的天线状结构。这些细胞器检测细胞外信号,将信号转导到细胞中,并在确保正确的细胞增殖、迁移和时空分化中发挥重要作用。不足为奇的是,纤毛的失调会导致各种疾病,包括癌症和纤毛病,这是由调节纤毛功能的基因突变引起的复杂疾病。纤毛的结构和功能受到多种机制的动态调控,其中E3泛素连接酶和去泛素酶起着至关重要的作用。这些酶通过泛素-蛋白酶体系统调节纤毛蛋白的降解和稳定。在这篇综述中,我们简要地强调纤毛在纤毛病和癌症中的作用;描述E3泛素连接酶和去泛素酶在纤毛发生、纤毛病和癌症中的作用;并强调一些E3泛素连接酶和去泛素酶是这些疾病的潜在治疗靶点。
Cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulation of cilia can cause various diseases, including cancer and ciliopathies, which are complex disorders caused by mutations in genes regulating ciliary function. The structure and function of cilia are dynamically regulated through various mechanisms, among which E3 ubiquitin ligases and deubiquitinases play crucial roles. These enzymes regulate the degradation and stabilization of ciliary proteins through the ubiquitin–proteasome system. In this review, we briefly highlight the role of cilia in ciliopathy and cancer; describe the roles of E3 ubiquitin ligases and deubiquitinases in ciliogenesis, ciliopathy, and cancer; and highlight some of the E3 ubiquitin ligases and deubiquitinases that are potential therapeutic targets for these disorders.
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