Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation.

ABSTRACT: Precise control of protein degradation is critical for life, yet how natural genetic variation affects this essential process is largely unknown. Here, we developed a statistically powerful mapping approach to characterize how genetic variation affects protein degradation by the ubiquitin-proteasome system (UPS). Using the yeast Saccharomyces cerevisiae, we systematically mapped genetic influences on the N-end rule, a UPS pathway in which protein N-terminal amino acids function as degradation-promoting signals. Across all 20 possible N-terminal amino acids, we identified 149 genomic loci that influence UPS activity, many of which had pathway- or substrate-specific effects. Fine-mapping of four loci identified multiple causal variants in each of four ubiquitin system genes whose prod

SUBMITTER: Collins MA 

PROVIDER: S-EPMC9634822 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature