[1]杨洋,樊赛军.LXXLL模体在雌激素受体信号通路中的作用及应用价值[J].国际放射医学核医学杂志,2014,38(1):22-32.[doi:10.3760/cma.j.issn 1673-4114.2014.01.006]
 Yang Yang,Fan Saijun.Role of LXXLL motif in modulation of estrogen receptor signaling and its potential application[J].International Journal of Radiation Medicine and Nuclear Medicine,2014,38(1):22-32.[doi:10.3760/cma.j.issn 1673-4114.2014.01.006]
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LXXLL模体在雌激素受体信号通路中的作用及应用价值(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
38
期数:
2014年第1期
页码:
22-32
栏目:
出版日期:
2014-01-25

文章信息/Info

Title:
Role of LXXLL motif in modulation of estrogen receptor signaling and its potential application
作者:
杨洋1 樊赛军2
1. 浙江省肿瘤医院放射治疗科, 杭州 310022;
2. 中国医学科学院放射医学研究所天津市分子核医学重点实验室, 天津 300192
Author(s):
Yang Yang1 Fan Saijun2
Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou 310022, China
关键词:
受体雌激素协同调节因子LXXLL模序共激活因子结合抑制剂模拟肽
Keywords:
ReceptorsestrogenCo-regulatorsLXXLL motifCo-activator binding inhibitorsMimetic Peptide
DOI:
10.3760/cma.j.issn 1673-4114.2014.01.006
摘要:
雌激素受体是核受体超家族中重要的一员,其与雌激素的结合在人类组织器官发育、新陈代谢以及许多疾病的发生和发展中起着重要的作用。协同调节因子是雌激素.雌激素受体信号转录传导途径中的一类重要调节分子,它们可以与雌激素受体直接结合,并作为协同激活因子上调或作为协同抑制因子降低雌激素受体的基因转录功能。蛋白分子结构分析发现,在协同调节因子与雌激素受体的相互作用中,其蛋白序列中含有的一段非常保守的富含亮氨酸的螺旋序列LXXLL模序(L指亮氨酸、x指任意氨基酸)扮演着重要角色,并在辅调节因子,特别是在协同激活因子中广泛地存在。深入研究DXXLL模序与雌激素受体相互作用的分子机制不仅有助于对LXXLL模序在雌激素受体.辅助调节因子蛋白之间相互作用中地位的理解,也为针对LXXLL模体与核受体的作用位点设计新的靶向药物奠定了基础。因此,该文简述了LXXLL模序在雌激素受体协同调节因子中存在的广泛性、LXXLL模序与雌激素受体相互作用的机制以及其在新药设计上的应用等相关方面的研究进展。
Abstract:
Estrogen receptor (ER), one member of the nuclear receptor superfamily, via binding to estrogen, plays important roles in development and metabolism of human tissues and organs as well as a number of diseases, such as cancer, obesity, diabetes and osteoporosis. Co-regulators, one important kind of factoYs in the ER transcriptional signaling, increase (as co-activators)or reduce (as co-repressors)ER- mediated transcriptional activity via direct and indirect binding to ER. Increasing evidence has revealed that a short α-helical sequence LXXLL motif (where L is leucine, X is any amino acid), widely present in many co-regulators, especially co-activators, plays an essential or necessary role in co-regulator interaction with ER. To explore the involved mechanism (s)will be helpful in understanding the critical role of LXXLL motif in the interaction of co-regulators and ER. This review briefly describes the potential roles of LXXLL motif in the involvement of ER co-regulators in modulation of ER signaling and underlying mechanisms as well as current progress in developing pharmaceutical agents that modulate ER-coregulator interaction via specifically targeting LXXLL motifs in therapy of hormone-associated cancers.

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备注/Memo

备注/Memo:
收稿日期:2013-11-20。
基金项目:国家自然科学基金(81071906,81172127)
通讯作者:樊赛军(Email:sjfan@irm-cams.ac.cn)
更新日期/Last Update: 1900-01-01