Functional Interplay between Androgen Receptor and novel Coactivators AATF, ZIP Kinase, and TSG101 in Transcription

转录中雄激素受体与新型共激活剂 AATF、ZIP 激酶和 TSG101 之间的功能相互作用

• 批准号: 79706039
• 负责人: Professor Dr. Karl Heinz Scheidtmann
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/79706039?language=en
• 关键词: Functional; Interplay; between; Androgen; Receptor

The Androgen receptor (AR) is a ligand-dependent transcription factor that plays a crucial role in the development and homeostasis of the prostate and in prostate cancer. We have identified transcription factor AATF, ZIP kinase, and ubiquitin binding protein TSG101 as transcriptional coactivators of AR. Of these, AATF seems to serve as adaptor or recruitment factor for ZIP kinase and TSG101 and, presumably, additional coactivators, ZIP kinase may regulate interactions or activities of other coactivators through phosphorylation, and TSG101 seems to play a role in regulating mono- and polyubiquitination of AR and other proteins. In the following program we would like to further elucidate the interplay and possible interdependence of the above mentioned coactivators in AR-mediated transcription. In particular, we want to (1) investigate the interdependence between AATF, ZIP kinase, and TSG101 by individual knockdown and subsequent ChIP and transcription analyses; (2) study the time course of assembly and disassembly of AR and its coactivators at enhancers and promoters; (3) identify substrates of ZIP kinase mediating its enhancing effect. The results will provide new insights into the regulation of AR-mediated transcription.

雄激素受体（AR）是一种配体依赖性转录因子，在前列腺和前列腺癌的发育和稳态中起着至关重要的作用。我们已经确定转录因子AATF，ZIP激酶，和泛素结合蛋白TSG 101作为AR的转录共激活因子。其中，AATF似乎充当ZIP激酶和TSG 101的适配器或募集因子，并且推测是额外的共激活因子，ZIP激酶可能通过磷酸化调节其他共激活因子的相互作用或活性，并且TSG 101似乎在调节AR和其他蛋白的单泛素化和多泛素化中起作用。在下面的程序中，我们将进一步阐明AR介导的转录中上述共激活因子的相互作用和可能的相互依赖性。具体而言，我们希望（1）通过个体敲除和随后的ChIP和转录分析来研究AATF、ZIP激酶和TSG 101之间的相互依赖性;（2）研究AR及其共激活因子在增强子和启动子处组装和分解的时间过程;（3）鉴定ZIP激酶介导其增强效应的底物。这些结果将为AR介导的转录调控提供新的见解。