泛素连接酶
泛素
癌变
生物
细胞生物学
肿瘤微环境
缺氧诱导因子
下调和上调
信号转导
翻译后调节
肿瘤进展
癌症研究
癌症
生物化学
磷酸化
遗传学
肿瘤细胞
基因
作者
Yijie Wang,Xiong Liu,Weixiao Huang,Junjie Liang,Yan Chen
标识
DOI:10.1016/j.pharmthera.2022.108303
摘要
Alterations in protein ubiquitination and hypoxia-inducible factor (HIF) signaling both contribute to tumorigenesis and tumor progression. Ubiquitination is a dynamic process that is coordinately regulated by E3 ligases and deubiquitinases (DUBs), which have emerged as attractive therapeutic targets. HIF expression and transcriptional activity are usually increased in tumors, leading to poor clinical outcomes. Reactive oxygen species (ROS) are upregulated in tumors and have multiple effects on HIF signaling and the ubiquitin system. A growing body of evidence has shown that multiple E3 ligases and UBDs function synergistically to control the expression and activity of HIF, thereby allowing cancer cells to cope with the hypoxic microenvironment. Conversely, several E3 ligases and DUBs are regulated by hypoxia and/or HIF signaling. Hypoxia also induces ROS production, which in turn modulates the stability or activity of HIF, E3 ligases, and DUBs. Understanding the complex networks between E3 ligase, DUBs, ROS, and HIF will provide insights into the fundamental mechanism of the cellular response to hypoxia and help identify novel molecular targets for cancer treatment. We review the current knowledge on the comprehensive relationship between E3 ligase, DUBs, ROS, and HIF signaling, with a particular focus on the use of E3 ligase or DUB inhibitors in cancer.
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