VHL As A Novel Substrate For Cytosolic Quality Control

描述（由申请人提供）：在他们的综合，这是必要的 蛋白质采用它们的功能性天然构象。蛋白质称为 分子伴侣的作用是促进快速和有效的折叠， proteins.然而，有些蛋白质由于突变或修饰， 以获得功能性折叠状态。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 蛋白质，但它们的确切功能尚不清楚。这个项目的目标 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和分子伴侣在 这个过程von Hippel-Lindau的野生型和肿瘤衍生突变体 (VHL)肿瘤抑制蛋白，一种已知的伴侣底物，将被用作 模型蛋白使用VHL来研究这个问题可能会产生新的目标 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.