斑点型锌指结构蛋白在肿瘤中的作用

Roles of SPOP in cancer

斑点型锌指结构蛋白(speckle-type POZ protein,SPOP)是E3泛素连接酶的底物接头蛋白,介导众多靶蛋白的泛素化修饰,从而参与调控细胞的多种功能。SPOP可以通过泛素-蛋白酶体途径降解下游靶蛋白,如PDK1、CDCA5、SLC7A1、ZBTB3、LATS1等,对肿瘤细胞的增殖、迁移、侵袭等进行调控;也可以通过非降解型泛素化修饰的方式作用于对应底物从而改变底物在癌症发生发展中的功能。鉴于SPOP在肿瘤中的重要作用,本文介绍了SPOP的结构,简述了肿瘤中SPOP基因表达调控的研究进展,回顾了近年来关于SPOP突变与异常表达在肿瘤中的功能研究。综上,SPOP可作为癌症药物治疗的潜在靶点。

Speckle-type POZ protein(SPOP) is an adapter protein of E3 ubiquitin ligase which mediates ubiquitination of many target proteins, and regulates various functions of cells. SPOP can degrade downstream target proteins, such as PDK1, CDCA5, SLC7A1, ZBTB3, and LATS1, through the ubiquitin-proteasome system, thereby regulating proliferation, migration, and invasion of tumor cells. It can also act on corresponding substrates through non-degradative ubiquitination to regulate the function of the substrate in cancer development. Given the important roles of SPOP in tumors, this paper introduces the structure of SPOP,briefly summarizes the research progress about the regulation of SPOP gene expression in tumors, and reviews recent studies of SPOP mutation and abnormal expression in tumors. Therefore, SPOP could serve as a potential drug target for the treatment of various types of cancer.