REGULATION AND FUNCTION OF NUCLEAR RECEPTOR COACTIVATORS
核受体共激活剂的调节和功能
基本信息
- 批准号:6708831
- 负责人:
- 金额:$ 19.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-02-15 至 2005-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Nuclear receptors mediate many hormone actions that regulate
important physiological processes in human and in higher
eukaryotic organisms. The binding of the lipophilic hormones to
nuclear receptors triggers conformational changes in the
receptors, leading to transcriptional activation of the receptors
and target gene stimulation. Recent studies have led to the
discovery of several nuclear receptor cofactors that can modulate
the transcriptional activity of nuclear receptors. These
cofactors are potential regulators of hormone actions. Two main
classes of nuclear receptor cofactors have been identified:
corepressors that promote transcriptional repression by
unliganded receptors and coactivators that enhance
transcriptional activation by liganded receptors. The event of
hormone-binding is believed to trigger dissociation of
corepressors from the receptors and recruitment of coactivators
to the receptors. The applicant's laboratory has recently
identified and cloned a new member of the nuclear receptor
coactivator family termed RAC3, which is also known as AIB1,
p/CIP, ACTR, and TRAM-1. The sequence of RAC3 is closely related
to that of SRC-1 and TIF2, two most potent nuclear receptor
coactivators. Currently, the biological relevance of RAC3 in
hormone signaling is still unclear, but importantly, RAC3 was
found to associate strongly with CBP/p300 in vivo and to be
overexpressed in several human cancer cells, suggesting a crucial
role of RAC3 in the regulation of cell growth and proliferation.
In order to better understand the mechanism of RAC3 action and
its role in hormone signaling, in this study we will continue to
investigate the structural and functional relationship of the
RAC3 protein. We will also investigate the role of RAC3 in
retinoic acid (RA)-mediated stem cell differentiation and control
of gene expression. Finally, we will identify and characterize
new RAC3-interacting proteins, thereby substantially expanding
our understanding of the biological function of RAC3 in living
cells. Together, these studies are critical for understanding
the function of the nuclear receptor coactivator RAC3 and its
role in hormone signaling. The functional interaction between
nuclear receptors and coactivators will serve as a model for
understanding transcriptional regulation of other transcriptional
activators. This project represents an important aspect of our
long-term directions and the results will provide insights for
development of future therapeutics that can control hormone-
regulated and -dysregulated cell growth and proliferation.
核受体介导许多激素活动,调节
人类和高等生物中的重要生理过程
真核生物。亲脂荷尔蒙与
核受体在细胞内触发构象变化
受体,导致受体的转录激活
和靶基因刺激。最近的研究导致了
几种可调节核受体辅因子的发现
核受体的转录活性。这些
辅因子是荷尔蒙活动的潜在调节者。两条主线
核受体辅助因子的种类已经被确定:
通过以下途径促进转录抑制的辅阻遏子
未连接的受体和辅助激活剂可增强
配体受体的转录激活作用。发生的事件
荷尔蒙结合被认为触发了细胞的解离
受体的辅抑制子和辅激活子的募集
到感受器。申请人的实验室最近
鉴定和克隆核受体的一个新成员
辅活化子家族称为RAC3,也被称为AIB1,
P/CIP、ACTR和电车-1。RAC3的序列密切相关
SRC-1和TIF2,这两个最强大的核受体
助活剂。目前,RAC3在中国的生物学意义
激素信号仍不清楚,但重要的是,RAC3
在体内被发现与CBP/p300强烈相关,并被认为是
在几个人类癌细胞中过表达,表明一个关键的
RAC3在调节细胞生长和增殖中的作用。
为了更好地了解RAC3的作用机制和
它在激素信号传递中的作用,在这项研究中我们将继续
调查结构和功能的关系
RAC3蛋白。我们还将调查RAC3在
维甲酸(RA)介导的干细胞分化与调控
关于基因表达的。最后,我们将确定和描述
新的RAC3相互作用蛋白,从而大大扩展
我们对RAC3在生活中的生物学功能的理解
细胞。总而言之,这些研究对于理解
核受体辅活化子RAC3的功能及其作用
在荷尔蒙信号中的作用。两国之间的功能互动
核受体和辅助激活剂将成为
了解其他转录因子的转录调控
激活剂。这个项目是我们的一个重要方面
长期方向和结果将为以下方面提供见解
未来可以控制荷尔蒙的疗法的发展-
调节和失调的细胞生长和增殖。
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Human ADA3 regulates RARalpha transcriptional activity through direct contact between LxxLL motifs and the receptor coactivator pocket.
- DOI:10.1093/nar/gkq269
- 发表时间:2010-09
- 期刊:
- 影响因子:14.9
- 作者:Li CW;Ai N;Dinh GK;Welsh WJ;Chen JD
- 通讯作者:Chen JD
Characterization of a novel small molecule subtype specific estrogen-related receptor alpha antagonist in MCF-7 breast cancer cells.
- DOI:10.1371/journal.pone.0005624
- 发表时间:2009-05-20
- 期刊:
- 影响因子:3.7
- 作者:Chisamore MJ;Cunningham ME;Flores O;Wilkinson HA;Chen JD
- 通讯作者:Chen JD
SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1.
SNF2 相关 CBP 激活蛋白 (SRCAP) 通过与 CARM-1 和 GRIP-1 的协同相互作用,充当类固醇受体介导的转录的共激活剂。
- DOI:10.1210/me.2003-0208
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:Monroy,MAlexandra;Schott,NatalieM;Cox,Linda;Chen,JDon;Ruh,Mary;Chrivia,JohnC
- 通讯作者:Chrivia,JohnC
Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin alpha3.
共激活因子 RAC3 的核定位由二分 NLS 和输入蛋白 alpha3 介导。
- DOI:10.1016/j.bbrc.2006.06.163
- 发表时间:2006
- 期刊:
- 影响因子:3.1
- 作者:Yeung,PercyLuk;Zhang,Aihua;Chen,JDon
- 通讯作者:Chen,JDon
The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor.
酵母 DNA 修复和 TFIIH 调节剂 MMS19 的人类同源物是雌激素受体 AF-1 特异性共激活剂。
- DOI:10.1074/jbc.m101041200
- 发表时间:2001
- 期刊:
- 影响因子:0
- 作者:Wu,X;Li,H;Chen,JD
- 通讯作者:Chen,JD
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
J DON CHEN其他文献
J DON CHEN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('J DON CHEN', 18)}}的其他基金
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6377993 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6769875 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6522917 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6166043 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6709853 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR BASIS OF ACUTE PROMYELOCYTIC LEUKEMIA
急性早幼粒细胞白血病的分子基础
- 批准号:
6802828 - 财政年份:2000
- 资助金额:
$ 19.99万 - 项目类别:
REGULATION AND FUNCTION OF NUCLEAR RECEPTOR COACTIVATORS
核受体共激活剂的调节和功能
- 批准号:
2752280 - 财政年份:1999
- 资助金额:
$ 19.99万 - 项目类别:
REGULATION AND FUNCTION OF NUCLEAR RECEPTOR COACTIVATORS
核受体共激活剂的调节和功能
- 批准号:
6150608 - 财政年份:1999
- 资助金额:
$ 19.99万 - 项目类别:
REGULATION AND FUNCTION OF NUCLEAR RECEPTOR COACTIVATORS
核受体共激活剂的调节和功能
- 批准号:
6350680 - 财政年份:1999
- 资助金额:
$ 19.99万 - 项目类别:
MOLECULAR ACTIONS OF NUCLEAR RECEPTOR COREPRESSOR SMRT
核受体 CorePressor SMRT 的分子作用
- 批准号:
6524609 - 财政年份:1998
- 资助金额:
$ 19.99万 - 项目类别:
相似海外基金
Induction of germ cell differentiation by a novel removable gene expression control system using riboswitch
使用核糖开关通过新型可移动基因表达控制系统诱导生殖细胞分化
- 批准号:
20K15669 - 财政年份:2020
- 资助金额:
$ 19.99万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Assembly of a dynamic spatio-temporal map of gene expression regulation during intestinal stem cell differentiation to enterocytes
肠道干细胞分化为肠上皮细胞过程中基因表达调控动态时空图的组装
- 批准号:
453309976 - 财政年份:2020
- 资助金额:
$ 19.99万 - 项目类别:
WBP Fellowship
Studies on the mechanism of gene expression that contributes to stem cell differentiation and homeostasis
干细胞分化和稳态的基因表达机制研究
- 批准号:
16K07396 - 财政年份:2016
- 资助金额:
$ 19.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The roles of THOC 5/Fms interacting protein, a member of mRNA export complex THOC, in the immediate-early gene expression induced by a cell differentiation signal.
THOC 5/Fms 相互作用蛋白(mRNA 输出复合物 THOC 的成员)在细胞分化信号诱导的早期基因表达中的作用。
- 批准号:
217461545 - 财政年份:2012
- 资助金额:
$ 19.99万 - 项目类别:
Research Grants
HTLV-1 hijacks T-cell differentiation/function by deregulatingHelios gene expression
HTLV-1通过解除Helios基因表达调控来劫持T细胞分化/功能
- 批准号:
23659484 - 财政年份:2011
- 资助金额:
$ 19.99万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Colon Cell Differentiation: NAB and MUC2 Gene Expression
结肠细胞分化:NAB 和 MUC2 基因表达
- 批准号:
7921237 - 财政年份:2009
- 资助金额:
$ 19.99万 - 项目类别:
Gene expression noise during cell differentiation and its regulation
细胞分化过程中的基因表达噪声及其调控
- 批准号:
20200006 - 财政年份:2008
- 资助金额:
$ 19.99万 - 项目类别:
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
Gene expression during stem cell differentiation
干细胞分化过程中的基因表达
- 批准号:
354066-2007 - 财政年份:2007
- 资助金额:
$ 19.99万 - 项目类别:
University Undergraduate Student Research Awards
Role of SUMOylation of Satb2 in the regulation of ES cell differentiation, gene expression and higher-order chromatin structure (P04)
Satb2 SUMO化在 ES 细胞分化、基因表达和高阶染色质结构调控中的作用 (P04)
- 批准号:
39236241 - 财政年份:2007
- 资助金额:
$ 19.99万 - 项目类别:
Collaborative Research Centres
GENE EXPRESSION DURING THE DUCT CELL DIFFERENTIATION IN SALIVARY GLANDS
唾液腺导管细胞分化过程中的基因表达
- 批准号:
17590154 - 财政年份:2005
- 资助金额:
$ 19.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)