PML蛋白翻译后修饰参与PML核体功能调节的研究进展

Post-translational Modifications of PML in Regulating the Functions of Nuclear Bodies——Review

早幼粒细胞白血病基因(promyelocytic leukemia,PML)编码的PML蛋白,作为抑癌因子在急性早幼粒细胞白血病以及多种癌症的发生及发展中扮演着重要的角色。PML蛋白在细胞中可发生多种形式的翻译后修饰,如SUMO化(SUMOylation)、泛素化(ubiquitination)、磷酸化(phosphorylation)和乙酰化(acetylation)修饰等。PML蛋白的这些修饰可直接影响PML核体(PML nuclear bodies,PML-NBs)的形成、DNA损伤修复、细胞凋亡等功能。异常修饰不仅可以引起血液系统肿瘤的发生,同时与肿瘤耐药有着密切关系。因此解析PML蛋白的翻译后修饰对PML核体形成及功能的影响和作用机制,以及相关血液系统肿瘤的预防和治疗均有重要的意义。本文就PML蛋白的翻译后修饰过程与PML核体功能间的关系作一综述,以期为相关肿瘤的药物治疗提供潜在的靶点。

The promyelocytic leukemia(PML)gene encoded PML protein as a tumor suppressor protein,plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia.Recent studies have indicated that there are a variety of post-translational modifications of the PML protein,such as SUMOylation,ubiquitination,phosphorylation,and acetylation in cells.These modifications of the PML protein can directly affect the formation of PML nuclear bodies(PML-NBs),repair DNA damage,and modulate cell apoptosis.Furthermore,the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors,but also are closely related to the drug-resistance of cancer.Therefore,investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs,thus contributing to the prevention and treatment of related hematopoietic tumors.In this review,the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.