REGULATION OF ANDROGEN RECEPTOR ACTIVITY IN THE PROSTATE
前列腺雄激素受体活性的调节
基本信息
- 批准号:6153870
- 负责人:
- 金额:$ 26.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-08-01 至 2004-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Adapted from the application) Our broad, long term objective is to characterize the molecular mechanisms by which the androgen receptor (AR) regulates transcriptional activation through its N-terminus. The AR is a hormone- dependent transcription factor involved in the regulation of both normal and malignant prostate cell growth. Although androgen hormones, such as dihydrotestosterone (DHT), act as the primary signal in activating AR's transcriptional regulatory functions, AR-mediated transcriptional activity is also controlled by associations with, as yet, unidentified regulatory cofactors involved in transcription. The N-terminus of AR contain several transcriptional activation functions, including AF-1a and AF-1b, and mutations in these domains reduce AR-dependent transcriptional activity. We propose that these domains provide surfaces that permit protein-protein contacts between the AR N-terminus and cofactors involved in transcriptional regulation. We propose that these domains provide surfaces that permit protein-protein contacts between the AR N-terminus and cofactors involved in transcriptional regulation. We will identify proteins that interact with the AR N-terminal activation domains using a modified yeast two-hybrid approach that is capable. Of isolating proteins that interact with transcriptional activators.. We will also define the effect of these AR-interact with transcriptional activators. We will also define the effect of these AR-interacting proteins on AR- transcriptional activity using a transient transfection proteins on AR- transcriptional activity using a transient transfection system designed to monitor AR-dependent transcriptional activation in cultured mammalian cells. Conceivably, alterations in the level of these AR N-terminal interacting proteins modulate AR activity., thereby, contributing to malignant AR-dependent prostate growth if altered in cancer. To test this hypothesis we will determine if the concentration of specific AR- interacting proteins varies in models of benign and malignant prostate growth using antibody and nucleic acid probes. Understanding of the communication between AR and the proteins that associate with the AR N-terminal transcriptional activation domain is fundamental to understanding the mechanism of AR-regulated gene expression and may reveal novel points of intervention to be exploited in the development of new therapies for AR-dependent malignancies, such as prostate cancer.
描述(根据申请改编)我们广泛的长期目标是表征雄激素受体(AR)通过其N-末端调节转录激活的分子机制。AR是参与调节正常和恶性前列腺细胞生长的激素依赖性转录因子。虽然雄激素,如双氢睾酮(DHT),作为激活AR的转录调节功能的主要信号,AR介导的转录活性也控制协会,迄今为止,未确定的参与转录的调节辅因子。AR的N-末端包含几种转录激活功能,包括AF-1a和AF-1b,这些结构域中的突变降低了AR依赖的转录活性。 我们建议,这些结构域提供的表面,允许蛋白质-蛋白质之间的AR N-末端和参与转录调控的辅因子的接触。我们建议,这些结构域提供的表面,允许蛋白质-蛋白质之间的AR N-末端和参与转录调控的辅因子的接触。我们将确定与AR N-末端激活结构域相互作用的蛋白质,使用修改后的酵母双杂交方法,能够。分离与转录激活因子相互作用的蛋白质。我们还将确定这些AR与转录激活因子相互作用的效果。我们还将使用瞬时转染系统确定这些AR相互作用蛋白对AR转录活性的影响,所述瞬时转染系统设计用于监测培养的哺乳动物细胞中的AR依赖性转录激活。 可以想象,这些AR N-末端相互作用蛋白水平的改变调节AR活性。因此,如果在癌症中改变,则会导致恶性AR依赖性前列腺生长。为了检验这一假设,我们将使用抗体和核酸探针确定特定AR相互作用蛋白的浓度在良性和恶性前列腺生长模型中是否变化。了解AR和与AR N-末端转录激活结构域相关的蛋白质之间的通信对于理解AR调节基因表达的机制是至关重要的,并且可以揭示在开发AR依赖性恶性肿瘤(例如前列腺癌)的新疗法中要利用的新的干预点。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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10.1016/j.celrep.2025.115527 - 发表时间:
2025-04-22 - 期刊:
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Matthew S. Rodeheffer
Brain-Derived Neurotrophic Factor Signaling Rewrites the Glucocorticoid Transcriptome via Glucocorticoid Receptor Phosphorylation
脑源性神经营养因子信号传导通过糖皮质激素受体磷酸化重写糖皮质激素转录组
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10.1128/mcb.01139-13 - 发表时间:
2013 - 期刊:
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W. M. Lambert;Chong;Thomas A. Neubert;Moses V. Chao;Michael J. Garabedian;Freddy D. Jeanneteau;Thomas A. Neubert;Moses V. Chao;Michael J. Garabedian;Freddy D. Jeanneteau - 通讯作者:
Freddy D. Jeanneteau
Sex differences in murine MASH induced by a fructose-palmitate-cholesterol-enriched diet
果糖 - 棕榈酸酯 - 胆固醇丰富饮食诱导的小鼠 MASH 中的性别差异
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10.1016/j.jhepr.2024.101222 - 发表时间:
2025-02-01 - 期刊:
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Lakshmi Arivazhagan;Sofie Delbare;Robin A. Wilson;Michaele B. Manigrasso;Boyan Zhou;Henry H. Ruiz;Kaamashri Mangar;Ryoko Higa;Emily Brown;Huilin Li;Michael J. Garabedian;Ravichandran Ramasamy;Kathryn J. Moore;Edward A. Fisher;Neil D. Theise;Ann Marie Schmidt - 通讯作者:
Ann Marie Schmidt
High dose methylprednisolone mediates YAP/TAZ-TEAD in vocal fold fibroblasts with macrophages
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10.1038/s41598-025-95459-z - 发表时间:
2025-03-31 - 期刊:
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Ryosuke Nakamura;Renjie Bing;Gary J. Gartling;Michael J. Garabedian;Ryan C. Branski - 通讯作者:
Ryan C. Branski
Modular Structure of Glucocorticoid Receptor Domains Is Not Equivalent to Functional Independence: STABILITY AND ACTIVITY OF THE STEROID BINDING DOMAIN ARE CONTROLLED BY SEQUENCES IN SEPARATE DOMAINS
- DOI:
10.1074/jbc.271.35.21430 - 发表时间:
1996-08-30 - 期刊:
- 影响因子:
- 作者:
Min Xu;Pradip K. Chakraborti;Michael J. Garabedian;Keith R. Yamamoto;S. Stoney Simons - 通讯作者:
S. Stoney Simons
Michael J. Garabedian的其他文献
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{{ truncateString('Michael J. Garabedian', 18)}}的其他基金
“Protection from MRSA lethality by inhibiting LXRα phosphorylation”
– 通过抑制 LXRα 磷酸化来防止 MRSA 致死 –
- 批准号:
10681027 - 财政年份:2023
- 资助金额:
$ 26.76万 - 项目类别:
Peptoid conjugates as inhibitors of androgen receptor dimerization and function in enzalutamide-resistant prostate cancer
类肽缀合物作为雄激素受体二聚化抑制剂及其在恩杂鲁胺耐药性前列腺癌中的功能
- 批准号:
9815670 - 财政年份:2019
- 资助金额:
$ 26.76万 - 项目类别:
Glucocorticoid receptor phosphorylation in endocrine adaptation to stress
糖皮质激素受体磷酸化在内分泌适应应激中的作用
- 批准号:
9883840 - 财政年份:2019
- 资助金额:
$ 26.76万 - 项目类别:
Targeting the glucocorticoid receptor in enzalutamide resistant prostate cancer
靶向恩杂鲁胺耐药性前列腺癌中的糖皮质激素受体
- 批准号:
9178221 - 财政年份:2016
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF ANDROGEN RECEPTOR ACTIVITY IN THE PROSTATE
前列腺雄激素受体活性的调节
- 批准号:
6381890 - 财政年份:2000
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF ANDROGEN RECEPTOR ACTIVITY IN THE PROSTATE
前列腺雄激素受体活性的调节
- 批准号:
6608814 - 财政年份:2000
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF ANDROGEN RECEPTOR ACTIVITY IN THE PROSTATE
前列腺雄激素受体活性的调节
- 批准号:
6524272 - 财政年份:2000
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
通过磷酸化调节糖皮质激素受体
- 批准号:
6350717 - 财政年份:1999
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
通过磷酸化调节糖皮质激素受体
- 批准号:
2736871 - 财政年份:1999
- 资助金额:
$ 26.76万 - 项目类别:
REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
通过磷酸化调节糖皮质激素受体
- 批准号:
6150653 - 财政年份:1999
- 资助金额:
$ 26.76万 - 项目类别:
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