MEN1基因生物学功能研究进展  

Progress on Biological Function of MEN1 Gene

作　　者：金光辉[1] 曾德泉[1] 徐斌[1] 

机构地区：[1]厦门大学医学院基础医学部,福建厦门361005

出　　处：《厦门大学学报（自然科学版）》2011年第2期437-444,共8页Journal of Xiamen University：Natural Science

基　　金：国家自然科学基金项目(81071926);厦门市科技计划项目(3502Z20104001)

摘　　要：MEN1基因是多发性内分泌肿瘤1型综合征(MEN1)的关键致病基因之一.其编码蛋白menin在细胞核中与混合谱系淋巴瘤基因(MLL)等大量关键转录因子相互作用,直接参与组蛋白甲基化修饰等表观遗传调控过程,对靶基因转录和细胞表型的维持起关键的调控作用.MEN1基因突变导致的menin表达或核转位异常将引起一系列信号通路紊乱,进而引起内分泌系统疾病如MEN1.近年来,随着研究的深入,发现menin参与调控的组蛋白3的赖氨酸4残基(H3K4)甲基化修饰与内分泌系统肿瘤以及非内分泌系统如血液系统肿瘤的发生密切相关;我们最近的研究结果显示,menin通过赖氨酸27残基(H3K27)组蛋白甲基化修饰调控的多效生长因子等关键信号通路是调节肺癌表型的重要机制之一,提示menin在内分泌系统之外的广泛的生物学作用.综述了本实验室及国际上关于menin生物学功能的经典及最近的研究,重点介绍menin在非内分泌系统肿瘤发生发展中的关键作用及其调控的组蛋白修饰特点、规律.同时根据我们新近的研究,提出menin在其他系统疾病发生中的可能作用.这些新发现将有助于进一步深入揭示menin介导的表观遗传学调控在疾病发生中的关键作用,为以menin为靶点的疾病治疗提供崭新思路.MEN1,one virulence gene of the multiple endocrine neoplasia type 1（MEN1）,encodes a protein referred to as menin.Menin plays a key role in the regulation of gene transcription and maintenance of cell phenotype via interacting with transcription factors which could directly influence histone modification in the nucleus,such as MLL（Mixed Lineage Leukemia）.Aberrant menin expression or nuclear translocation caused by MEN1 mutation results in unregulation of signal pathways and occurrence of endocrine system diseases such as MEN1.Recent studies show that the function of menin to epigenetic histone modifications is associated with endocrine neoplasia and non-endocrine neoplasia such as hematological tumors;Interestingly,our recent results show that menin regulates pleiotropic growth factor（PTN） through H3K27me3,which is an important mechanism in lung cancer phenotype,suggesting wide biological roles of menin.Here we review the previous and the recent progresses on the biological function of menin,especially on the role of menin in the development of non-endocrine neoplasia and the pattern of histone modifications.These findings indicate the potential effects of menin on other diseases.The new knowledge will help to further reveal the menin-mediated epigenetic regulation in diseases,and could also provide new ideas for therapeutic interventions against disease targeted on menin.

关 键 词：多发性内分泌肿瘤综合征 MENIN 混合谱系淋巴瘤基因 PCG 

分 类 号：Q291[生物学—细胞生物学]