Mechanisms of substrate selection in ER associated protein degradation (P15)

内质网（ER）的错误折叠蛋白穿过ER膜进入胞质溶胶，在胞质溶胶中它们被多聚泛素化并被蛋白酶体降解。这一过程被称为ER相关蛋白降解（ERAD）或逆向易位。ERAD的机制知之甚少。在这个项目中，我们想回答的问题，蛋白质是如何选择的逆易位和逆易位是如何调节。为此，我们将结合联合收割机在体外重建实验与纯化的蛋白质和实验在完整的细胞使用酵母酿酒酵母和裂殖酵母粟酒裂殖酵母作为模式生物。

Misfolded proteins of the endoplasmic reticulum (ER) are moved across the ER membrane into the cytosol where they are poly-ubiquitinated and degraded by the proteasome. This process is called ER associated protein degradation (ERAD) or retrotranslocation. The mechanism of ERAD is poorly understood. In this project, we want to answer the questions of how proteins are selected for retrotranslocation and how retrotranslocation is regulated. To this end, we will combine in vitro reconstitution experiments with purified proteins and experiments in intact cells using the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe as model organisms.