Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 26, Issue 14, Pages 2596-2608Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E15-03-0168
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Funding
- ETH Research Grant [07 10-1]
- Swiss National Science Foundation [31003A_127098]
- Swiss National Science Foundation (SNF) [31003A_127098] Funding Source: Swiss National Science Foundation (SNF)
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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.
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