人类 E3 泛素连接酶：促进和抑制 SARS-CoV-2 感染。
Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.
机构信息
Broad Institute of MIT and Harvard, Cambridge, MA, U.S.A.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, U.S.A.
出版信息
Biochem Soc Trans. 2024 Oct 30;52(5):2009-2021. doi: 10.1042/BST20230324.
E3 ubiquitin ligases regulate the composition of the proteome. These enzymes mono- or poly-ubiquitinate their substrates, directly altering protein function or targeting proteins for degradation by the proteasome. In this review, we discuss the opposing roles of human E3 ligases as effectors and targets in the evolutionary battle between host and pathogen, specifically in the context of SARS-CoV-2 infection. Through complex effects on transcription, translation, and protein trafficking, human E3 ligases can either attenuate SARS-CoV-2 infection or become vulnerabilities that are exploited by the virus to suppress the host's antiviral defenses. For example, the human E3 ligase RNF185 regulates the stability of SARS-CoV-2 envelope protein through the ubiquitin-proteasome pathway, and depletion of RNF185 significantly increases SARS-CoV-2 viral titer (iScience (2023) 26, 106601). We highlight recent advances that identify functions for numerous human E3 ligases in the SARS-CoV-2 life cycle and we assess their potential as novel antiviral agents.
E3 泛素连接酶调节蛋白质组的组成。这些酶可以单泛素化或多泛素化它们的底物，直接改变蛋白质功能或靶向蛋白质被蛋白酶体降解。在这篇综述中，我们讨论了人类 E3 连接酶作为效应物和靶标在宿主和病原体之间的进化斗争中的相反作用，特别是在 SARS-CoV-2 感染的背景下。通过对转录、翻译和蛋白质运输的复杂影响，人类 E3 连接酶可以减弱 SARS-CoV-2 感染，或者成为病毒利用的弱点，以抑制宿主的抗病毒防御。例如，人类 E3 连接酶 RNF185 通过泛素蛋白酶体途径调节 SARS-CoV-2 包膜蛋白的稳定性，而 RNF185 的耗竭显著增加了 SARS-CoV-2 病毒滴度（iScience（2023）26，106601）。我们强调了最近的进展，这些进展确定了许多人类 E3 连接酶在 SARS-CoV-2 生命周期中的功能，并评估了它们作为新型抗病毒药物的潜力。
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