Hsp110 protein chaperone function in yeast

描述(申请人提供)：热休克蛋白(HSPs)在细胞生物学中具有双重作用；它们是抵御细胞毒性应激的第一道防线，在正常生长条件下紧密整合到信号和调节通路中。热休克蛋白的一部分，包括热休克蛋白70和热休克蛋白90，作为分子伴侣，在底物蛋白质生命周期的多个阶段，从生物发生、定位和稳定，到激活和降解，都可能是必需的。蛋白伴侣在包括缺血和肿瘤发生在内的多种病理生理条件下被诱导，并被认为促进了癌蛋白的稳定性和活性，如v-src激酶和p53肿瘤抑制因子。Hsp110类伴侣蛋白是一个知之甚少的Hsp70家族，存在于所有真核生物中，在人类中具有未知功能的组织特异性亚型。面包师的酵母Hsp110同源基因由SSE1和SSE2基因编码，对它们的功能知之甚少。这项建议试图通过提出三个具体的问题来开始了解Hsp110伴侣的细胞作用：1)Sse1如何与酵母Hsp70 Ssa1合作运作，2)Sse1如何与Hsp90合作通过酵母细胞完整性途径参与信号转导，以及3)Sse1如何通过与基本转录复合体中介的相互作用独立于Hsp90发挥作用？酵母中的这些特定的研究线路将作为预测Hsp110可能促进哺乳动物细胞哪些过程的模型。

DESCRIPTION (provided by applicant): Heat shock proteins (Hsps) play dual roles in cellular biology; they are the first line of defense against cytotoxic stresses, and are tightly integrated into signaling and regulatory pathways under normal growth conditions. A subset of Hsps, including Hsp70 and Hsp90, act as molecular chaperones, and may be required at multiple stages during a substrate protein's lifetime, ranging from biogenesis, localization, and stability, to activation and degradation. Protein chaperones are induced during numerous pathophysiological conditions including ischemia and tumorigenesis, and are known to facilitate stability and activity of oncoproteins such as v-src kinase and the p53 tumor suppressor. The Hsp110 class of chaperones is a poorly understood Hsp70 relative and is present in all eukaryotes, with tissue-specific isoforms of unknown function in humans. The baker's yeast Hsp110 homolog is encoded by the SSE1 and SSE2 genes, and little is known about their function. This proposal seeks to begin to understand the cellular roles of Hsp110 chaperones by asking three specific questions: 1) How does Sse1 operate in partnership with the yeast Hsp70 Ssa1, 2) How does Sse1 participate in signal transduction through the yeast cell integrity pathway in collaboration with the chaperone Hsp90, and 3) How does Sse1 function independently of Hsp90 through interaction with the essential transcriptional complex Mediator? These specific lines of investigation in yeast will serve as a model for predicting which processes Hsp110 may facilitate in mammalian cells.