Protein degradation corrects for imbalanced subunit stoichiometry in OST complex assembly

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 pos...

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Bibliographic Details
Published in:Molecular biology of the cell 2015-07, Vol.26 (14), p.2596-2608
Main Authors: Mueller, Susanne, Wahlander, Asa, Selevsek, Nathalie, Otto, Claudia, Ngwa, Elsy Mankah, Poljak, Kristina, Frey, Alexander D, Aebi, Markus, Gauss, Robert
Format: Article
Language:English
Subjects:
Endoplasmic Reticulum-Associated Degradation
Hexosyltransferases - metabolism
Kinetics
Mass Spectrometry
Membrane Proteins - metabolism
Saccharomyces cerevisiae - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E15-03-0168