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泛素特异性肽酶(USP8)的致癌作用及其作为癌症治疗靶点的信号通路。

The oncogenic role of ubiquitin specific peptidase (USP8) and its signaling pathways targeting for cancer therapeutics.

机构信息

Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, China.

Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Arch Biochem Biophys. 2021 Apr 15;701:108811. doi: 10.1016/j.abb.2021.108811. Epub 2021 Feb 16.

Abstract

USP8 is a deubiquitinating enzyme in the family of ubiquitin-specific proteases (USPs) which can remove ubiquitin from the substrate and protect the substrate from degradation. The upregulated or mutated USP8 becomes hyperactivated and stabilizes numerous oncogenes or proto-oncogenes leading to cancer progression and survival by activating multiple signaling pathways. Moreover, USP8 inhibition is also important to overcome anticancer drug-resistant. This review is the first study to find, combine, analyze, and represent the multiple oncogenic signaling pathways with their downstream and upstream regulation activated or enhanced by USP8, which will help the researchers to find any therapeutic strategy for drug discovery by inhibiting or suppressing the multi-targeted USP8.

摘要

USP8 是泛素特异性蛋白酶(USP)家族中的一种去泛素化酶,可从底物上去除泛素并防止底物降解。上调或突变的 USP8 变得过度活跃,并通过激活多种信号通路,稳定众多癌基因或原癌基因,从而促进癌症的进展和存活。此外,USP8 的抑制对于克服抗癌药物耐药性也很重要。这是第一项研究,旨在寻找、结合、分析和表示由 USP8 激活或增强的多个致癌信号通路及其下游和上游调控,这将有助于研究人员通过抑制或抑制多靶向 USP8 来找到任何药物发现的治疗策略。

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