类泛素蛋白ISG15及其共价酶修饰系统与肿瘤

Ubiquitin-like protein ISG15 and its modification system in tumor

干扰素刺激基因15(interferon-stimulated gene 15,ISG15)编码的ISG15蛋白是最早发现的类泛素修饰蛋白。不仅干扰素和病毒感染能诱导该基因的表达,一些抗肿瘤药物也能刺激ISG15的表达。近年来,ISG15及其修饰系统与肿瘤的关系备受关注。研究证实,ISG15的激活酶E1即UBE1L与某些肿瘤的抑制有关,而其他一些成分如ISG15解聚酶UBP43则与肿瘤发生发展有关。此外,ISG15高表达与肿瘤的转移有关,ISG15对化疗药物的敏感性也有影响。本文较为全面地阐述ISG15及其修饰系统在肿瘤抑制或发生发展中的生物学作用,这将增强对ISG15与肿瘤关系的基础性认识,并为发展新的肿瘤靶向性治疗提供理论依据。

Interferon-stimulated gene 15（ISG15） encodes a protein named ISG15,which is the first identified ubiquitin-like protein.The expression of ISG15 is induced not only by type I IFN and viral infection,but also by some anticancer drugs.Recently,it was found that ISG15 and its modification system were also involved in tumor suppression or tumorigenesis.Enzyme such as ubiquitin-activating enzyme E1-like（UBE1L） appears tumor-suppressive,while other enzymes such as de-ISGylation enzyme,UBP43 promotes tumorigenesis.Overexpression of ISG15 has been observed in metastasis of some malignant tumors.Alteration of ISG15 expression can affect the chemosensitivity of some chemotherapy drugs.We reviewed the biological effect of ISG15 in tumor-related target,which will provide fundamental knowledge of ISG15 in cancer research and may provide new insight for tumor therapy.