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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 changes of tumor-associated protein subcellular localization can affect its protein structure and biological function, which is closely related to tumorigenesis, development and prognosis. Aberrant phosphorylation, acetylation, and ubiquitination modify the subcellular localization of tumor-associated proteins, which in turn can alter downstream target gene expression and related cell signaling pathways, an important factor in tumorigenesis. Anti-cancer drugs acting on post-translational modifications of proteins reverse the abnormal subcellular localization of tumor-associated proteins, thereby inhibiting tumor cell migration and promoting apoptosis. In this study, the effects of phosphorylation, acetylation and ubiquitination on the subcellular location of these proteins were summarized by using p53, forkhead box protein O1 (FOXO1) and p27 as an example. Cell localization of anti-cancer drugs mechanism of action, and discusses the protein subcellular localization of clinical malignant tumor diagnosis, prognosis and drug effects prediction effect of great significance.