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泛素化在发育和疾病中的交汇点。

Ubiquitylation at the crossroads of development and disease.

机构信息

Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, California 94720, USA.

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.

出版信息

Nat Rev Mol Cell Biol. 2018 Jan;19(1):59-70. doi: 10.1038/nrm.2017.83. Epub 2017 Sep 20.

Abstract

Human development requires intricate cell specification and communication pathways that allow an embryo to generate and appropriately connect more than 200 different cell types. Key to the successful completion of this differentiation programme is the quantitative and reversible regulation of core signalling networks, and post-translational modification with ubiquitin provides embryos with an essential tool to accomplish this task. Instigated by E3 ligases and reversed by deubiquitylases, ubiquitylation controls many processes that are fundamental for development, such as cell division, fate specification and migration. As aberrant function or regulation of ubiquitylation enzymes is at the roots of developmental disorders, cancer, and neurodegeneration, modulating the activity of ubiquitylation enzymes is likely to provide strategies for therapeutic intervention.

摘要

人类的发展需要精细的细胞特异性和通讯途径,使胚胎能够产生并适当连接 200 多种不同的细胞类型。成功完成这一分化程序的关键是核心信号网络的定量和可逆调节,而泛素化的翻译后修饰为胚胎提供了完成这一任务的重要工具。E3 连接酶引发的泛素化,以及去泛素化酶的逆转,控制着许多对发育至关重要的过程,如细胞分裂、命运特化和迁移。由于泛素化酶的功能异常或调节失常是发育障碍、癌症和神经退行性疾病的根源,因此调节泛素化酶的活性可能为治疗干预提供策略。

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