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

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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.