Molly Dolan Ball State University, Avery Kirshbaum Ball State University
Faculty Sponsor(s): Eric Rubenstein Ball State UniversityConditions ranging from hypercholesteremia to premature aging are linked to ineffective protein degradation. Enzymes involved in both protein synthesis and degradation are present at the ER membrane. Proteins entering the ER pass through a channel called the translocon. Cells have developed multiple quality control mechanisms at the translocon, whereby proteins stalling in the channel are degraded. The ubiquitin ligase Hrd1 targets a subset of proteins that stall in the translocon for proteasomal degradation. Likewise, the protease Ste24 also cleaves other translocon-stalled proteins. Despite the important roles of Hrd1 and Ste24, individually deleting the genes encoding either has no effect on yeast growth rate. However, combined loss of Ste24 and Hrd1 slows growth. We hypothesized that this growth phenotype was due to loss of Hrd1 and Ste24 function at the translocon. However, because Hrd1 and Ste24 have other roles, it was also possible that the phenotype was due to loss of Hrd1 and Ste24 function outside the translocon. To determine if the phenotype depends on Hrd1’s translocon-associated function, yeast were engineered to lack both Ste24 and Usa1, a cofactor needed for Hrd1 to target aberrant ER luminal or transmembrane proteins but not translocon-associated proteins. To determine if compromised quality control generally impairs growth when Ste24 is absent, we created strains lacking Ste24 and the protein quality control enzyme Doa10. The slow growth phenotype persists in strains that lack Ste24 and any of these quality control proteins. Thus, loss of Ste24 sensitizes yeast to defects in multiple protein quality control pathways.
When & Where
Irwin Library 3rd Floor