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USP1 去泛素化酶在癌症发病机制和治疗中的作用。

The role of USP1 deubiquitinase in the pathogenesis and therapy of cancer.

机构信息

Department of Molecular Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.

Department of Oncohematology, RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.

出版信息

Acta Biochim Pol. 2023 Jun 12;70(2):219-231. doi: 10.18388/abp.2020_6636.

Abstract

Ubiquitin-specific protease 1 (USP1) is an important deubiquitinating enzyme (DUB) involved in the maintenance of genome integrity, cell cycle, and cell homeostasis. USP1 overexpression is a characteristic feature of various cancers, correlating with a poor prognosis. The review summarizes the recent knowledge in understanding the role of deubiquitinase USP1 in the stabilization of oncoproteins and tumor suppressors, as a critical event in cancer development and progression. The putative mechanisms of USP1 involvement in some prevalent human cancers are discussed. The numerous data demonstrate that inhibition of USP1 suppresses the proliferation and viability of malignant cells, sensitizes them to radiation and increases their sensitivity to various chemo- therapeutic agents, which opens up new opportunities for combined therapy of malignant neoplasms.

摘要

泛素特异性蛋白酶 1(USP1)是一种重要的去泛素化酶(DUB),参与维持基因组完整性、细胞周期和细胞内稳态。USP1 的过表达是各种癌症的一个特征,与预后不良相关。综述总结了目前关于去泛素酶 USP1 在稳定癌蛋白和肿瘤抑制因子中的作用的最新认识,这是癌症发展和进展中的一个关键事件。讨论了 USP1 参与一些常见人类癌症的潜在机制。大量数据表明,抑制 USP1 可抑制恶性细胞的增殖和活力,使它们对辐射敏感,并增加它们对各种化疗药物的敏感性,这为恶性肿瘤的联合治疗开辟了新的机会。

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