干扰素刺激基因15的研究进展

Advances in research on interferon-stimulated gene 15

干扰素刺激基因(interferon-stimulated genes,ISGs)是一类快速的干扰素刺激反应基因,主要参与抵抗病毒、细菌入侵及免疫功能调节。干扰素刺激基因15(interferon-stimulated gene 15,ISG15)是ISGs家族成员之一,也是第一个被鉴定出来的泛素样蛋白(ubiquitin-like protein,UBL),它既可以以游离形式存在,也可以与底物结合,对底物进行ISG化(ISGylation)修饰。ISG化修饰能够竞争性阻断底物的泛素化降解,进而影响底物的生物学功能。目前确证的ISG15底物约一百余种,它们的功能涉及病毒复制、细胞增殖、细胞周期调控、凋亡、自噬、DNA损伤修复、蛋白质翻译等诸多方向。本文将对近10年ISG15在对抗病毒侵袭、免疫功能调节和参与肿瘤发生、发展等方向的研究进展进行总结综述。

Interferon stimulated genes(ISGs)are the rapid interferon stimulated response genes,mainly involved in resisting to virus and bacteria invasion and immunomodulatory function.ISG15 is a member of the ISGs family and the first ubiquitin-like protein(UBL)to be identified.ISG15 exists either in a free form orcan be covalently conjugated onto target proteins via an enzymatic cascade to compete blocking of ubiquitination degradation of substrates.Furthermore,the biological functions of substrates are affected.To date,there are about hundreds of putative targets of ISGylation have been identified.Many functions of ISGylation have emerged that implicate it in multiple cellular processes,such as cell proliferation,cell cycle regulation,protein translation,apoptosis,autophagy,DNA damage repair,virus replicationand immunomodulatory.This review will summarizethe advances in research of ISG15 in resisting virus replication,immunomodulatory and tumorigenesis in the past decade.