蛋白亚细胞定位与肿瘤关系的研究进展

Progress in the association between protein subcellular localization and tumor progression

肿瘤相关蛋白亚细胞定位的改变可影响其蛋白结构和生物学功能,与肿瘤的发生、发展及预后密切相关。异常的磷酸化、乙酰化和泛素化修饰可影响肿瘤相关蛋白的亚细胞定位,进而改变下游靶基因表达及相关细胞信号通路,这是诱导肿瘤发生的重要因素。作用于蛋白翻译后修饰的抗癌药物可逆转肿瘤相关蛋白的异常亚细胞定位,进而抑制肿瘤细胞迁移,并促进细胞凋亡。本文以p53、叉头框蛋白O1(forkhead box protein O1,FOXO1)和p27等分子为例,总结了磷酸化、乙酰化和泛素化修饰对这些蛋白亚细胞定位的影响,以及目前影响蛋白亚细胞定位的抗癌药物的作用机制,并讨论了蛋白亚细胞定位对临床恶性肿瘤诊断、预后判断和药物作用效果预测具有的重要意义。

The change of subcellular localization of tumor-related proteins affects the protein structure and biological function, which is closely related to tumorigenesis, tumor progression and prognosis. Aberrant phosphorylation, acetylation and ubiquitination lead to the subcellular localization change of tumor-related proteins, subsequently disrupt the down-stream target gene expression and the related cell signal pathways, which is an important factor for tumorigenesis. The anti-cancer drugs targeting post-translational protein modification can reverse the abnormal subcellular localization of tumor-related proteins, so as to suppress the migration of tumor cells, and induce the apoptosis of tumor cells. This paper reviews the recent studies regarding the effects of phosphorylation, acetylation and ubiquitination on subcellular localization of tumor-related proteins such as p53, p27 and forkhead box protein O1 （FOXO1）, and summarizes the molecular mechanisms of subcellular localization change induced by anti-cancer drugs, furthermore discusses the great significance of protein subcellular localization in clinical tumor diagnosis and the pridiction of prognosis and the drug effect.