ROLE OF HSP90 IN POLARIZED CELL MORPHOGENESIS IN SCEREVISIAE & C ALBICANS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。丰富的细胞质分子伴侣Hsp 90及其辅助分子伴侣对类固醇受体、致癌酪氨酸激酶和参与信号传导途径和细胞周期控制的其他多种蛋白质的活性至关重要。热休克蛋白90和辅分子伴侣在ATP依赖性途径中相互作用，促进底物蛋白折叠至其天然状态。Hsp 90抑制剂已被证明可以减缓白色念珠菌产生耐药性的能力。我们的工作重点是表征热休克蛋白90与酵母特异性蛋白的相互作用，首先在S。cerevisiae和C.白色念珠菌我们开发了一种检测方法，使我们能够分离天然酵母热休克蛋白90复合物，含有已知的辅伴侣蛋白和新的推定客户蛋白。使用肽质量图谱，我们确定了四个新的热休克蛋白90相互作用的蛋白质，并确认了另一种相互作用。在我们的努力，以确定如何热休克蛋白90与不同的客户端蛋白质相互作用，我们将检查热休克蛋白90和这些和其他蛋白质的共同伴侣的相互作用，以开发一个更全面的图片在体内的热休克蛋白90分子机器的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The abundant cytoplasmic molecular chaperone Hsp90 and its co-chaperones are critical for the activity of steroid receptors, oncogenic tyrosine kinases and additional diverse proteins involved in signaling pathways and cell cycle control. Hsp90 and co-chaperones interact in an ATP-dependent pathway that facilitates the folding of substrate proteins to their native state. Hsp90 inhibitors have been shown to slow the ability of Candida albicans to develop drug resistance. A focus of our work is to characterize the interaction of Hsp90 with yeast-specific proteins, first in S. cerevisiae and then in C. albicans. We developed an assay that allows us to isolate native yeast Hsp90 complexes that contain both known co-chaperone proteins and novel presumed client proteins. Using peptide mass mapping we identified four novel Hsp90 interacting proteins and confirmed another interaction. In our efforts to determine how Hsp90 interacts with diverse client proteins, we will examine the interaction of Hsp90 and co-chaperones with these and other proteins in order to develop a more comprehensive picture of the in vivo mechanisms of the Hsp90 molecular machine.