Regulation, dislocation and elimination of membrane proteins of different eukaryotic organelles: Function of the proteasome and its helpers (Regulation, Dislokation und Eliminierung von Membranproteinen verschiedener eukaryonter Organellen: Die Funktion d

不同真核细胞器膜蛋白的调节、错位和消除：蛋白酶体及其辅助物的功能

• 批准号: 5374617
• 负责人: Professor Dr. Dieter H. Wolf
• 金额: --
• 依托单位: Abteilung für Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2003-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5374617?language=en
• 关键词: Regulation; dislocation; elimination; membrane; proteins

It has been shown that endoplasmic reticulum (ER) bound enzymes are regulated, and malfolded plasma membrane proteins are retained and eliminated from the ER via the ubiquitin-proteasome system. Furthermore it has been demonstrated that the mammalian apoptotic inducer Bax, which integrates into the outer mitochondrial membrane, also induces the programmed cell death program in yeast. The anti-apoptotic protein Bcl-XL rescues mammalian and yeast cells from Bax-induced apoptosis. Bax levels are regulated by the proteasome. In a first project the dislocation and subsequent elimination of the mammalian cystic fibrosis transmembrane conductance regulator (CFTR) in yeast and, for a comparison, a mutated yeast relative of CFTR, the pleiotropic drug resistance protein Pdr5, both polytopic membrane proteins, by the proteasome and new helper proteins will be analyzed. In a second project the mechanism of regulation of the pro-apoptotic protein Bax of the outer mitochondrial membrane by Bcl-XL and proteasomal proteolysis will be unraveled. The studies will extend our understanding of quality control of polytopic plasma membrane proteins and help to better understand the human disease cystic fibrosis. Furthermore understanding of regulation of the mitochondrial membrane located protein Bax will give insights into control of apoptosis. In addition the study will give general insights into the proteasomal elimination of membrane proteins of different organelles.

已经表明，内质网（ER）结合酶的调节，并通过泛素-蛋白酶体系统保留和消除错误折叠的质膜蛋白。此外，已经证明整合到线粒体外膜中的哺乳动物细胞凋亡诱导剂Bax也诱导酵母中的程序性细胞死亡程序。抗细胞凋亡蛋白Bcl-XL拯救哺乳动物和酵母细胞免于凋亡诱导的细胞凋亡。Bax水平受蛋白酶体调节。在第一个项目中，将分析酵母中哺乳动物囊性纤维化跨膜传导调节因子（CFTR）的错位和随后的消除，以及作为比较，突变的酵母相对于CFTR，多效性耐药蛋白Pdr5，两种多位膜蛋白，通过蛋白酶体和新的辅助蛋白。在第二个项目中，将阐明Bcl-XL和蛋白酶体蛋白水解调节线粒体外膜促凋亡蛋白Bax的机制。这些研究将扩展我们对多位质膜蛋白质质量控制的理解，并有助于更好地了解人类疾病囊性纤维化。此外，了解线粒体膜定位蛋白Bax的调控将有助于了解细胞凋亡的控制。此外，这项研究将提供一般的见解蛋白酶体消除不同细胞器的膜蛋白。