过刊浏览

一个功能丰富的转录调控分子——下游调控元件拮抗分子

伏紫冰¹, 段旭博^1,2, 李丽娜¹, 雷小康¹, 蒋烨¹, 王晨¹, 许寒晓^1,2, 张银连¹, 姜交华¹, 柴睿超¹, 贾熙华¹, 于常海^1,*

¹星形胶质细胞功能研究实验室，北京大学神经科学研究所；北京大学医学部基础医学院神经生物系；国家卫生和计划生育委员会/教育部神经科学重点实验室，北京 100191；²贵州医科大学人体解剖学教研室，贵阳 550025

摘要

下游调控元件拮抗分子(downstream regulatory element antagonist modulator, DREAM)与钙衰蛋白(Calsenilin)和钾通道辅助亚基(potassium channel interacting protein 3, KChIP3)，三者同属于神经钙感受器蛋白(neuronal calcium sensor, NCS)家族，由同一基因编码，但亚细胞定位不同且执行不同功能，其中DREAM定位于细胞核，有4个EF手型结构域(EF-hand-like motifs)能与钙离子可逆结合，诱导蛋白空间结构变化，结合到多种基因的下游调控元件(downstream regulatory element, DRE)位点发挥基因转录调节作用。DREAM在中枢神经系统(central nervous system, CNS)尤其是小脑皮层中高表达，通过调控N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor, NMDAR)影响学习和记忆，也参与阿尔兹海默症发病、炎症反应、血栓形成。随着更多DREAM新功能的发现，其在CNS中的生物功能受到更多关注。本文回顾DREAM的发现历史，分析该蛋白的结构功能特点、组织分布，讨论了近些年来在DREAM入核的调控、以及特有的钙依赖的基因调控机理方面研究进展，重点关注了DREAM -强啡肽原(prodynorphin, PDYN)-强啡肽(dynorphin, DYN)通路调节慢性疼痛的可能机制。

关键词： DREAM; 转录调节 ; 疼痛 ; DRE位点 ; 钙信号

分类号：Q42;R741

DREAM: a multifunctional transcriptional regulator

FU Zi-Bing¹, DUAN Xu-Bo^1,2, LI Li-Na¹, LEI Xiao-Kang¹, JIANG Ye¹, Wang Chen¹, XU Han-Xiao^1,2, ZHANG Yin-Lian¹, JIANG Jiao-Hua¹, CHAI Rui-Chao¹, JIA Xi-Hua¹, YU Albert Cheung Hoi^1,*

¹Laboratory of Functional Study of Astrocytes, Peking University Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University; Key Laboratory for Neuroscience, Ministry of Education; National Health and Family Planning Commission, Beijing 100191, China；²Department of Human Anatomy, Guizhou Medical University, Guiyang 550025, China

Abstract

DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3 (potassium channel interacting protein 3) belong to the neuronal calcium sensor (NCS) superfamily, which transduces the intracellular calcium signaling into a variety of activities. They are encoded by the same gene locus, but have distinct subcellular locations. DREAM was first found to interact with DRE (downstream regulatory element) site in the vicinity of the promoter of prodynorphin gene to suppress gene transcription. Calcium can disassemble this interaction by binding reversibly to DREAM protein on its four EF-hand motifs. Apart from having calcium dependent DRE site binding, DREAM can also interact with other transcription factors, such as cAMP responsive element binding protein (CREB), CREB-binding protein (CBP) and cAMP responsive element modulator (CREM), by this concerted actions, DREAM extends the gene pool under its control. DREAM is predominantly expressed in central nervous system with its highest level in cerebellum, and accumulating evidence demonstrated that DREAM might play important roles in pain sensitivity. Novel findings have shown that DREAM is also involved in learning and memory processes, Alzheimer’s disease and stroke. This mini-review provides a brief introduction of its discovery history and protein structure properties, focusing on the mechanism of DREAM nuclear translocation and gene transcription regulation functions.

Key words: DREAM; transcriptional regulation ; pain ; DRE site ; calcium signal

收稿日期：2017-05-07　　录用日期：2017-08-18

通讯作者：于常海　　E-mail: achy@hsc.pku.edu.cn

DOI: 10.13294/j.aps.2017.0053

引用本文：

伏紫冰, 段旭博, 李丽娜, 雷小康, 蒋烨, 王晨, 许寒晓, 张银连, 姜交华, 柴睿超, 贾熙华, 于常海. 一个功能丰富的转录调控分子——下游调控元件拮抗分子[J]. 生理学报 2017; 69 (5): 703-714.

FU Zi-Bing, DUAN Xu-Bo, LI Li-Na, LEI Xiao-Kang, JIANG Ye, Wang Chen, XU Han-Xiao, ZHANG Yin-Lian, JIANG Jiao-Hua, CHAI Rui-Chao, JIA Xi-Hua, YU Albert Cheung Hoi. DREAM: a multifunctional transcriptional regulator. Acta Physiol Sin 2017; 69 (5): 703-714 (in Chinese with English abstract).