VHL As A Novel Substrate For Cytosolic Quality Control

描述(申请人提供)：综合后，势在必行 蛋白质采用其功能性的天然构象。一种名为 分子伴侣有助于快速有效地折叠 蛋白质。然而，由于突变或修饰，一些蛋白质不能 以达到功能性折叠状态。这些错误折叠的蛋白质可能是 对细胞有害，因此是降解的目标。近年来， 分子伴侣与错误折叠的降解有关 蛋白质，但它们的确切功能尚不清楚。这个项目的目标是 是用酿酒酵母作为模式生物来探索 错误折叠的蛋白质降解及其分子伴侣在蛋白质降解中的作用 这一过程。Von Hippel-Lindau野生型和肿瘤来源的突变体 已知的伴侣底物(VHL)肿瘤抑制蛋白将被用作 模型蛋白质。用VHL来研究这个问题可能会产生新的靶点 用于VHL相关癌症的治疗干预。

DESCRIPTION (provided by applicant): Upon their synthesis, it is imperative that proteins adopt their functional, native conformations. Proteins called molecular chaperones act to facilitate the rapid and efficient folding of proteins. Some proteins, however, due to mutation or modification, are unable to attain a functional folded state. These misfolded proteins may be deleterious to the cell and are thus targeted for degradation. In recent years, molecular chaperones have been implicated in the degradation of misfolded proteins, but their precise function remains unclear. The goal of this project is to use the yeast Saccharomyces cerevisiae as a model organism to explore misfolded protein degradation and the role that molecular chaperones play in this process. Wild-type and tumor-derived mutants of the von Hippel-Lindau (VHL) tumor suppressor protein, a known chaperone substrate, will be used as model proteins. The use of VHL to study this problem may result in new targets for therapeutic intervention in VHL-related cancers.