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

研究表明，内质网(ER)结合酶受到调控，错误折叠的质膜蛋白通过泛素-蛋白酶体系统从内质网中保留和清除。此外，研究还表明，整合到线粒体膜外的哺乳动物细胞凋亡诱导剂Bax也可以诱导酵母细胞的程序性死亡程序。抗凋亡蛋白BclxL可将哺乳动物和酵母细胞从Bax诱导的细胞凋亡中解救出来。Bax水平受蛋白酶体调节。在第一个项目中，将分析蛋白酶体和新的辅助蛋白对哺乳动物囊性纤维化跨膜电导调节因子(CFTR)在酵母中的错位和随后的消除，作为比较，还将分析CFTR的突变近亲、多效性耐药蛋白Pdr5，这两种膜蛋白都是由蛋白酶体和新的辅助蛋白组成的。在第二个项目中，我们将解开BclxL和蛋白酶体蛋白分解对线粒体膜外膜促凋亡蛋白Bax的调节机制。这些研究将扩大我们对多聚体质膜蛋白质量控制的理解，有助于更好地理解人类疾病囊性纤维化。此外，了解线粒体膜定位蛋白Bax的调控将有助于对细胞凋亡的控制。此外，这项研究还将对不同细胞器的膜蛋白的蛋白酶体消除提供一般性的见解。

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.