title: Protein degradation corrects for imbalanced subunit stoichiometry in OST complex assembly.
abstract: Protein degradation is essential for cellular homeostasis. We developed a sensitive approach to examining protein degradation rates in Saccharomyces cerevisiae by coupling a SILAC approach to selected reaction monitoring (SRM) mass spectrometry. Combined with genetic tools, this analysis made it possible to study the assembly of the oligosaccharyl transferase complex. The ER-associated degradation machinery compensated for disturbed homeostasis of complex components by degradation of subunits in excess. On a larger scale, protein degradation in the ER was found to be a minor factor in the regulation of protein homeostasis in exponentially growing cells, but ERAD became relevant when the gene dosage was affected, as demonstrated in heterozygous diploid cells. Hence the alleviation of fitness defects due to abnormal gene copy numbers might be an important function of protein degradation.
authors.affiliation: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Functional Genomics Center Zurich, UZH/ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Asa
authors.initials: A
authors.lastname: Wahlander
authors.affiliation: Functional Genomics Center Zurich, UZH/ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Selevsek
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, ETH Zürich, CH-8092 Zurich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Otto
authors.affiliation: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Elsy Mankah
authors.initials: EM
authors.lastname: Ngwa
authors.affiliation: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Kristina
authors.initials: K
authors.lastname: Poljak
authors.affiliation: Department of Biotechnology and Chemical Technology, Aalto University, FI-00076 Aalto, Finland.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Frey
authors.affiliation: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland robert.gauss@micro.biol.ethz.ch markus.aebi@micro.biol.ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Aebi
authors.affiliation: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland robert.gauss@micro.biol.ethz.ch markus.aebi@micro.biol.ethz.ch.
authors.forename: Robert
authors.initials: R
authors.lastname: Gauss
mesh_terms: D060746:Endoplasmic Reticulum-Associated Degradation; D006602:Hexosyltransferases / Q000378:metabolism*; D007700:Kinetics; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D006602:Hexosyltransferases; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase