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泛素连接酶在癌症中的作用及其临床潜力。

Ubiquitin ligases in cancer: Functions and clinical potentials.

机构信息

Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.

Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY, USA.

出版信息

Cell Chem Biol. 2021 Jul 15;28(7):918-933. doi: 10.1016/j.chembiol.2021.04.008. Epub 2021 May 10.

Abstract

Ubiquitylation, a highly regulated post-translational modification, controls many cellular pathways that are critical to cell homeostasis. Ubiquitin ligases recruit substrates and promote ubiquitin transfer onto targets, inducing proteasomal degradation or non-degradative signaling. Accumulating evidence highlights the critical role of dysregulated ubiquitin ligases in processes associated with the initiation and progression of cancer. Depending on the substrate specificity and biological context, a ubiquitin ligase can act either as a tumor promoter or as a tumor suppressor. In this review, we focus on the regulatory roles of ubiquitin ligases and how perturbations of their functions contribute to cancer pathogenesis. We also briefly discuss current strategies for targeting or exploiting ubiquitin ligases for cancer therapy.

摘要

泛素化是一种高度调控的翻译后修饰,控制着许多对细胞稳态至关重要的细胞通路。泛素连接酶招募底物并促进泛素转移到靶标上,诱导蛋白酶体降解或非降解信号。越来越多的证据强调了失调的泛素连接酶在与癌症发生和进展相关的过程中的关键作用。根据底物特异性和生物学背景,泛素连接酶可以作为肿瘤促进剂或肿瘤抑制剂发挥作用。在这篇综述中,我们重点讨论了泛素连接酶的调节作用,以及它们功能的失调如何导致癌症的发病机制。我们还简要讨论了针对泛素连接酶或利用泛素连接酶进行癌症治疗的当前策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4932/8286310/a57ce6e23e4f/nihms-1693436-f0001.jpg

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