RhoB的翻译后修饰与细胞命运  

Post-translational Modifications of RhoB in Cell Fate Determination

作　　者：曾涛玲 王洪睿[1] Zeng Tao-Ling;Wang Hong-Rui(School of Life Sciences,Xiamen University,Xiamen 361102,China)

机构地区：[1]厦门大学生命科学学院,厦门361102

出　　处：《生物化学与生物物理进展》2023年第5期900-906,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(32070761);福建省自然科学基金(2022J05006)资助项目。

摘　　要：RhoB作为Rho家族的一员,其生物学活性和蛋白质水平的调控与其他成员有着较大的不同,在肿瘤的发生发展中也起着独特的作用。RhoB作为抑癌蛋白在肿瘤的靶向治疗上受到越来越多的关注,然而在有些类型的肿瘤中RhoB却起着促进肿瘤生长的作用,其中的分子机理还不清楚,亟待研究阐明。可逆的翻译后修饰是快速与精细调控RhoB功能的重要分子机制,对于维持正常细胞的生长、抑制细胞的早期癌变及肿瘤的发生发展至关重要。本文就RhoB翻译后修饰的研究,特别是其泛素化和SUMO化修饰之间的转化在肿瘤细胞命运决定中的作用进行综述,以期为探索RhoB的调控与肿瘤发生发展的机制,以及以RhoB为靶点的癌症治疗提供线索和思路。As a special member of the Rho family,RhoB exhibits distinct biological activities and plays a unique role in tumorigenesis,and its protein levels are tightly regulated compared with other family members.Acting as a tumor suppressor,RhoB has attracted increasing attention in targeted cancer therapy.However,RhoB has been reported to promote development of certain types of tumors,in which the underlying molecular mechanisms remain unclear.In this article we summarize the studies on post-translational modifications of RhoB,particularly its ubiquitination and sumoylation,and their roles in determining the fate of tumor cells.Under normal physiological conditions,RhoB is targeted to ubiquitination and degradation by E3 ubiquitin ligase Smurf1,therefore maintaining relatively low protein levels of RhoB for cell survival.In response to single strand DNA damage,activated Chk1 phosphorylates Smurf1 to induce its self-degradation,resulting an accumulation of RhoB.Meanwhile,RhoB is also phosphorylated by Chk1,leading to dissociation of RhoB from plasma membrane.Phosphorylated RhoB is further sumoylated by SUMO E3 PIAS1 in cytosol,which is required for translocation of TSC2 to lysosomes to inhibit mTORC1 activity and subsequent initiation of autophagy.Hence,RhoB plays a pivotal role in determining cell fate by switching between its ubiquitination and sumoylation.These multiple layers of regulation enable RhoB to execute appropriate cellular responses in different cellular states and environmental conditions.Further exploring the regulatory mechanisms of RhoB in tumor development may provide valuable clues and ideas for cancer treatment by targeting RhoB.

关 键 词：RHOB 翻译后修饰 脂化修饰 磷酸化 泛素化 SUMO化 

分 类 号：Q26[生物学—细胞生物学] Q28