揭示去泛素化酶在几种癌症顺铂耐药中的作用。

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sun-Kyu Jin, Kwang-Hyun Baek
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引用次数: 0

摘要

使用铂类药物治疗癌症是化疗中最常用的方法之一。特别是,顺铂通过与DNA碱基结合阻断DNA合成,从而通过多种途径导致细胞凋亡,从而诱导细胞死亡。然而,化疗的主要障碍是耐药性。为了克服耐药性,泛素-蛋白酶体系统(UPS)已成为一个潜在的治疗靶点。UPS是一个关键的信号通路,通过将泛素附着在底物上,从而导致蛋白酶体降解,从而调节大多数细胞蛋白。相反,去泛素化酶(DUBs)从底物中去除标记的泛素并抑制降解,从而维持蛋白质稳态。近年来,人们对DUB的底物进行了鉴定,并对其细胞机制进行了研究,目前使用DUB抑制剂的治疗方法正在临床试验中。然而,DUB对顺铂反应的机制尚不清楚。本文就dub对顺铂治疗作用的研究进展进行综述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the role of deubiquitinating enzymes on cisplatin resistance in several cancers
The use of platinum-based drugs in cancer treatment is one of the most common methods in chemotherapy. Especially, cisplatin induces cell death by interrupting DNA synthesis by binding to the DNA bases, thereby leading to the apoptosis via multiple pathways. However, the major hurdle in chemotherapy is drug resistance. To overcome drug resistance, the ubiquitin-proteasome system (UPS) has emerged as a potential therapeutic target. The UPS is a pivotal signaling pathway that regulates the majority of cellular proteins by attaching ubiquitin to substrates, leading to proteasomal degradation. Conversely, deubiquitinating enzymes (DUBs) remove tagged ubiquitin from the substrate and inhibit degradation, thereby maintaining proteostasis. Recently, studies have been conducted to identify the substrates of DUBs and investigated the cellular mechanisms, and now the development of therapeutics using DUB inhibitors is in clinical trials. However, the mechanism of the DUB response to cisplatin remains still unclear. In this review, we summarize the research reported on the function of DUBs responding to cisplatin.
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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