调控PTEN表达和活性的研究进展  

Advances on regulation of PTEN expression and activity

作　　者：祁闪闪 杨李 卢文婕 孙鸣 宋娜[1] 陈智[1] 熊昊[1] QI Shan-shan;YANG Li;LU Wen-jie;SUN Ming;SONG Na;CHEN Zhi;XIONG Hao(Department of Hematology and Oncology,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,China)

机构地区：[1]华中科技大学同济医学院武汉儿童医院血液肿瘤科,湖北武汉430015

出　　处：《中国病理生理杂志》2020年第12期2289-2293,共5页Chinese Journal of Pathophysiology

基　　金：湖北省卫计委面上项目(No.WJ2017M1952);武汉市卫计委面上项目(No.WX13B19)。

摘　　要：人第10号染色体缺失的磷酸酶及张力蛋白同源基因(phosphatase and tensin homologue deleted on chromosome ten,PTEN)是一个经典的抑癌基因,位于染色体10q23.3,其编码区含有1209个碱基,编码一个含有403个氨基酸的蛋白。PTEN蛋白含有4个重要的功能区域:(1)N末端结构域,是PTEN蛋白N端的32个氨基酸组成的短肽,含有核定位序列;(2)催化结构域,由第7~185位氨基酸残基在内的179个氨基酸组成,负责PTEN的去磷酸化活性;(3)C2结构域,由第186~351位氨基酸残基在内的186个氨基酸组成,主要介导PTEN蛋白插入和锚定到脂质双分子层;(4)尾区,包含第352~403位氨基酸残基在内的肽段,该区域富含丝氨酸和苏氨酸,参与调控PTEN的稳定性和磷脂酶活性。PTEN尾区最后4个(第400~403位)氨基酸即ITKV,被称为PDZ结合基序(PDZ-binding motif,PDZ-BM),这一肽段介导PTEN与含有PDZ结构域的蛋白的相互结合。Phosphatase and tensin homologue deleted on chromosome ten(PTEN)is a classical tumor suppressor which possesses lipid and protein phosphatase activity.PTEN acts as an important negative regulator of tumorigenesis in a phosphatidylinositol 3-kinase(PI3K)inhibition-dependent manner as well as PI3K-independent manner.PTEN has been shown to affect a broad spectrum of biological functions,including cell proliferation,survival,migration and genomic stability.Although mutations and deletions of PTEN are frequent in human tumors,novel regulation mechanisms of PTEN expression and activity,by changes in PTEN protein levels,location and enzymatic activity,have also attracted significant attention.Herein,we review the current knowledge on the regulation of PTEN expression and activity by epigenetic silencing,transcriptional repression and post-translational modifications in human tumors.

关 键 词：PTEN蛋白 磷脂酰肌醇3-激酶 表达调控 活性调控 

分 类 号：R363[医药卫生—病理学] R73[医药卫生—基础医学]