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雌、孕激素受体的转录激活与调控

辛启亮, 邱静涛, 崔胜, 夏国良, 王海滨

中国农业大学生物学院，农业生物技术国家重点实验室，北京 100193；中国科学院动物研究所，干细胞与生殖生物学国家重点实验室，北京 100101

摘要

雌激素受体与孕激素受体都是类固醇激素受体这一进化上高度保守的转录因子家族的重要成员。当雌、孕激素受体分别与其配体在细胞浆中结合后进入核内，与靶基因上特异的DNA响应元件结合，并适时募集一些辅助转录因子，诱导特定基因转录表达，影响靶细胞的功能活动。雌、孕激素受体的转录活性还因其在蛋白翻译后所发生的不同修饰而改变。蛋白翻译后的修饰种类繁多。经典的修饰为丝/苏氨酸和酪氨酸残基的磷酸化修饰。近些年的研究发现，泛素化与类泛素化修饰对激素受体的稳定性、在亚细胞定位及其对辅助因子的募集等方面都发挥重要作用，并最终影响激素受体的转录活性。本文旨在对国内外近几年关于雌、孕激素受体的转录活性调控及其在早期妊娠中的生理意义进行综述，这将有助于理解雌、孕激素作用异常相关的女性生殖疾病。

关键词： 雌激素受体; 孕激素受体; 翻译后修饰; 转录激活; 共辅助因子; 早期妊娠

分类号：Q492;R339.2

Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation

XIN Qi-Liang, QIU Jing-Tao, CUI Sheng, XIA Guo-Liang, WANG Hai-Bin

State Key Laboratory for Agro-biotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China； State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

Abstract

Estrogen receptor (ER) and progesterone receptor (PR) are two important members of steroid receptors family, an evolutionarily conserved family of transcription factors. Upon binding to their ligands, ER and PR enter cell nucleus to interact with specific DNA element in the context of chromatin to initiate the transcription of diverse target genes, which largely depends on the timely recruitment of a wide range of cofactors. Moreover, the interactions between steroid hormones and their respective receptors also trigger post-translational modifications on these receptors to fine-tune their transcriptional activities. Besides the well-known phosphorylation modifications on tyrosine and serine/threonine residues, recent studies have identified several other covalent modifications, such as ubiquitylation and sumoylation. These post-translational modifications of steroid receptors affect its stability, subcellular localization, and/or cofactor recruitment; eventually influence the duration and extent of transcriptional activation. This review is to focus on the recent research progress on the transcriptional activation of nuclear ER and PR as well as their physiological functions in early pregnancy, which may help us to better understand related female reproductive diseases.

Key words: Estrogen receptor; progesterone receptor; post-translational modifications; transcriptional activation; cofactors; early pregnancy

收稿日期：2016-02-02　　录用日期：2016-06-08

通讯作者：王海滨　　E-mail: haibin.wang@vip.163.com

引用本文：

辛启亮, 邱静涛, 崔胜, 夏国良, 王海滨. 雌、孕激素受体的转录激活与调控[J]. 生理学报 2016; 68 (4): 435-454.

XIN Qi-Liang, QIU Jing-Tao, CUI Sheng, XIA Guo-Liang, WANG Hai-Bin. Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation. Acta Physiol Sin 2016; 68 (4): 435-454 (in Chinese with English abstract).