MOLECULAR CHAPERONES AND SIGNAL TRANSDUCTION

描述(摘自申请者的摘要)：类固醇激素 受体，其中包括人类雄激素受体，维持在一个 与HSP90相关的激素结合前的非活动状态和 其他分子伴侣。卡普兰博士提出的研究将 关注分子伴侣Ydj1p在这一过程中的作用，a 与Hsp70一起在蛋白质组装中发挥作用的DNAJ同源物 反汇编事件。先前的生化研究表明，Hsp70 在Hsp90与糖皮质激素的组装中起直接作用 受体在需要ATP的过程中，Ydj1p具有类似的作用 已被体内的遗传学研究证实。建议进行的研究包括 将使用遗传和生化方法的组合来解剖 这一过程旨在了解Ydj1p在受体中的作用 激活。这些研究将在酵母细胞中表达 人类雄激素受体。 这项建议的具体目的是：1)。定义YDJ1的结构域 在人类雄激素受体激活中起作用。2)。要确定 Ydj1p在雄激素受体激活过程中发挥作用， 和3)。为了表征DNAJ/Hsp70伴侣对如何在 高等真核生物中雄激素受体的激活。

DESCRIPTION (Adapted from the applicant's abstract): Steroid hormone receptors, among them the human androgen receptor, are maintained in an inactive state prior to hormone binding by association with hsp90 and other molecular chaperons. The studies proposed by Dr. Caplan will focus on the role of the molecular chaperon Ydj1p in this process, a DnaJ homolog that functions together with Hsp70 in protein assembly and disassembly events. Previous biochemical studies indicated that Hsp70 plays a direct role in the assembly of Hsp90 with the glucocorticoid receptor in a process requiring ATP, and a similar role of Ydj1p has been confirmed by genetic studies in vivo. Studies are proposed which will use a combination of genetic and biochemical approaches to dissect this process with a view to understanding the role of Ydj1p in receptor activation. These studies will be performed with yeast cells expressing human androgen receptor. The specific aims of this proposal are: 1). To define the domains of YDJ1 that function in human androgen receptor activation. 2). To determine where Ydj1p functions in the process of androgen receptor activation, and 3). To characterize how a DnaJ/Hsp70 chaperon pair functions in the activation of the androgen receptor in higher eukaryotes.