Protein degradation corrects for imbalanced subunit stoichiometry in OST complex assembly
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Date
2015-07-05
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
26 (14)
Pages / Article No.
2596 - 2608
Publisher
American Society for Cell Biology
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02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
03408 - Aebi, Markus (emeritus) / Aebi, Markus (emeritus)