EBP1 CONTROL OF PROSTATE CANCER CELL GROWTH

描述（改编自申请人的摘要）：申请人的小组有 最近克隆了一种新的蛋白质Ebp 1，它与细胞质相互作用， 结构域的heregulin/neuregulin受体，ErbB 3。Ebp 1异位表达 抑制雄激素依赖性激活雄激素应答报告基因 结构。本建议的目的是通过以下方式了解该机制： Ebp 1抑制雄激素受体（AR）介导的转录。第一 具体的目的是：（1）确定Ebp 1调节AR介导的 来自不同野生型和天然雄激素应答的转录 启动子和内源基因;（2）确定Ebp 1的能力， 抑制AR转录辅激活因子的活性;（3）确定Ebp 1 可抑制ErbB 2诱导AR介导的反式激活。第二个目标 申请人将：（1）确认并扩展AR和Ebp 1的观察结果 物理关联和（2）确定AR和Ebp 1所需的区域 蛋白质结合生成的缺失构建体将用于 确定Ebp 1对AR介导的转录的抑制作用， 细胞生长与这种蛋白结合AR的能力有关。

DESCRIPTION (adapted from the applicant's abstract): The applicant's group has recently cloned a new protein, Ebp1, which interacts with the cytoplasmic domain of the heregulin/neuregulin receptor, ErbB3. Ectopic expression of Ebp1 inhibits androgen dependent activation of androgen responsive reporter constructs. The purpose of this proposal is to understand the mechanism by which Ebp1 inhibits androgen receptor (AR) mediated transcription. The first specific aim will: (1) determine the ability of Ebp1 to modulate AR-mediated transcription from different wild type and natural androgen-responsive promoters and from endogenous genes; (2) determine the ability of Ebp1 to inhibit the activity of AR transcriptional coactivators; (3) determine if Ebp1 can inhibit ErbB2 induction of AR-mediated transactivation. In the second aim the applicant will: (1) confirm and extend the observation that AR and Ebp1 physically associate and (2) determine the regions of AR and Ebp1 needed for protein-protein binding. Deletion constructs generated will be used to determine if the inhibitory effects of Ebp1 on AR-mediated transcription and cell growth are related to the ability of this protein to bind AR.