视网膜母细胞瘤结合锌指蛋白1调控肥胖和肿瘤信号通路研究综述  

A review of RIZ1 regulation of the signal pathways in obesity and tumors

作　　者：谢小雷[1] 江佩欣 张敬鸿 莫骏健 吴可凡 曾康逸 XIE Xiaolei;JIANG Peixin;ZHANG Jinghong;MO Junjian;WU Kefan;ZENG Kangyi(Molecular Diagnosis Center,Qingyuan People's Hospital,Guangdong province/The Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan 511518,China)

机构地区：[1]广州医科大学附属第六医院/广东省清远市人民医院分子诊断中心,清远511518

出　　处：《上海交通大学学报（医学版）》2023年第1期114-119,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(82000806);广东省基础与应用基础研究省企联合基金(2021A1515220118);广东省医学科研基金(A2020553);清远市科技计划项目(2018B036)。

摘　　要：视网膜母细胞瘤结合锌指蛋白1(retinoblastoma-interacting zinc finger protein 1,RIZ1)基因,又称PRDM2(positive regulatory domain 2)基因,是PRDM基因家族一员,其蛋白序列包含1个PR结构域、1个核激素受体结合基序、8个锌指结构域和1个视网膜母细胞瘤蛋白(retinoblastoma protein,Rb)相互作用基序。RIZ1主要定位于细胞核内,在核内发挥转录抑制因子、基因调控、蛋白质-蛋白质相互作用等功能。RIZ1是代谢通路的重要参与者,其通过调控代谢相关基因影响基础代谢,抑制肥胖的形成;RIZ1功能突变或含量不足与多种肿瘤发生发展相关,其通过激活下游致癌基因或调控代谢参与肿瘤进程。RIZ1通过v-akt鼠科胸腺瘤病毒癌基因同源物Ⅲ(v-akt murine thymoma viral oncogene homolog 3,AKT3)、胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1),以及作为协同激活剂等方式分别调控AKT/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、IGF-1、雌激素这3条肿瘤和肥胖相关分子信号通路。3条分子通路功能有差异且其下游分子存在交叉,提示RIZ1在不同年龄、性别和器官中的作用可能不同。详细研究RIZ1与RIZ2在代谢进程中的调控作用有助于全面了解RIZ1参与肥胖和肿瘤形成的机制。未来基于RIZ1靶点进行诊断研究或功能恢复可能对代谢性疾病和肿瘤的诊断和治疗有重要意义。Retinoblastoma-interacting zinc finger protein 1(RIZ1)gene,also known as positive regulatory domain 2(PRDM2),is a member of the PRDM gene family whose protein sequence consists of a PR domain,a nuclear hormone receptor binding motif,eight zinc finger domains,and an Rb(retinoblastoma protein)interacting motif.RIZ1 is mainly localized in the nucleus,where it plays a role in transcriptional repressor,gene regulation,protein-protein interactions,and other functions.RIZ1 is an important participant in the metabolic pathway,which affects basal metabolism and inhibits the development of obesity by regulating metabolism-related genes;functional mutations or insufficient content of RIZ1 are associated with the development of a variety of tumors,which participate in tumor processes by activating downstream oncogenes or regulating metabolism.RIZ1 regulates three molecular signal pathways,AKT(v-akt murine thymoma viral oncogene homolog)/mTOR(mechanistic target of rapamycin kinase),IGF-1(insulin-like growth factor 1),and estrogen,in tumors and obesity through AKT3 and IGF-1,respectively,or acting as a co-activator.The functional differences of the three molecular pathways and the crossover of their downstream molecules suggest that RIZ1 may function differently in different ages,genders,and organs.The study of the regulatory role of RIZ1 and RIZ2 in metabolic processes can help to fully understand the mechanism of RIZ1 involvement in obesity and tumor formation.In the future,diagnostic research or functional recovery based on RIZ1 targets may be of great significance for the diagnosis and treatment of metabolic diseases and tumor.

关 键 词：视网膜母细胞瘤结合锌指蛋白1 PRDM2基因 代谢 肥胖 肿瘤 信号通路 

分 类 号：R393[医药卫生—基础医学]