EBP1 CONTROL OF PROSTATE CANCER CELL GROWTH

描述(改编自申请人的摘要)：申请人所在的小组有 最近克隆了一种新的蛋白质Ebp1，它与细胞质相互作用 Hereglin/neuRegin受体的结构域ErbB3。Ebp1基因的异位表达 抑制雄激素反应报告基因的雄激素依赖性激活 构造。这项建议的目的是通过以下方式了解该机制 其中Ebp1抑制雄激素受体(AR)介导的转录。第一 特定的目的将：(1)确定Ebp1对AR介导的调节能力 不同野生型和自然雄激素反应基因的转录 启动子和内源基因；(2)决定Ebp1基因表达的能力 抑制AR转录共激活因子的活性；(3)检测Ebp1 能抑制ErbB2诱导的AR介导的反式激活。在第二个目标中 申请人将：(1)确认并扩展AR和Ebp1的观察结果 物理关联和(2)确定需要的AR和Ebp1区域 蛋白质-蛋白质结合。生成的删除构造将用于 确定Ebp1对AR介导的转录和转录的抑制作用 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.