葡萄糖调节蛋白78研究进展  

Glucose Regulated Protein 78 kD

作　　者：吴逸园[1] 杨业鹏[2] 李载权[1,2] 

机构地区：[1]北京大学医学部生物化学与分子生物学系,北京100191 [2]北京大学医学部放射医学系,北京100191

出　　处：《生理科学进展》2009年第2期135-141,共7页Progress in Physiological Sciences

基　　金：国家自然科学基金(30470846);国家教育部留学回国人员启动基金;国家自然科学基金委创新群体项目基金(30621002)资助课题

摘　　要：葡萄糖调节蛋白78(glucose regulated protein 78kD,GRP78)又称免疫球蛋白重链结合蛋白(immunoglobulin heavy chain binding protein,Bip),是位于内质网上重要的分子伴侣,属热休克蛋白70家族的一员,GRP78分子及其DNA分子序列结构在许多生物物种中高度保守。GRP78在内质网中参与阻止内质网新生肽聚集、调节内质网钙稳态、抗内质网相关性细胞凋亡,以及启动未折叠蛋白反应等细胞生命过程。GRP78基因启动子上存在内质网应激反应元件(ERSE)和cAMP反应元件(CRE)等特殊的顺式作用元件,特异性转录因子ATF6等与GRP78启动子上顺式作用元件发生动态结合,从而调节GRP78基础性或诱导性转录表达。近年来发现,GRP78与脂肪肝、肿瘤和神经系统等疾病的发生发展密切相关,GRP78生物学功能的研究已经引起生物学家们的广泛重视。One of the most important chaperons located on endoplasmic reticulum, GRP78, referred as BiP（ immunoglobulin heavy chain binding protein）, belongs to heat shock protein 70 family. GRP78 exists conservatively among a wide variety of biological species, and acts as a central regulator of endoplasmic reticulum （ER） functions, participating in ER protein folding and assembly process, and maintaining ER Ca^2＋ homeostasis, unfolded protein response and specific anti-apoptotic actions. Specific regulatory cis-elements such as ER stress response element （ERSE） and cAMP response element （CRE） were identified on the promoter of GRP78. Dynamic epigenic interactions between specific transcription factors such as AFT6 and regulatory elements in GRP78 gene promoter might contribute to human GRP78 constitutive or inducible transcription, resulting from some physiological and pathological stresses. Recently, cellular relationship between GRP78 expression and hepatosteatosis, cancer and nervous system diseases in human was underwent further clinical and biochemical research, which will benefit to human beings.

关 键 词：葡萄糖调节蛋白78 GRP78-ERdj3循环 甲基化酶依赖单启动子分析 

分 类 号：Q71[生物学—分子生物学]