Proteasome subunit ?1 overexpression preferentially drives canonical proteasome biogenesis and enhances stress tolerance in yeast.

ABSTRACT: The 26S proteasome conducts the majority of regulated protein catabolism in eukaryotes. At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two ?-rings sandwiched between two ?-rings. Whereas canonical CPs contain ?-rings with seven subunits arranged ?1-?7, a non-canonical CP in which a second copy of the ?4 subunit replaces the ?3 subunit occurs in both yeast and humans. The mechanisms that control canonical versus non-canonical CP biogenesis remain poorly understood. Here, we have repurposed a split-protein reporter to identify genes that can enhance canonical proteasome assembly in mutant yeast producing non-canonical ?4-?4 CPs. We identified the proteasome subunit ?1 as an enhancer of ?3 incorporation, and find that elevating ?1 protein levels preferentially drives canonical CP assembly under conditions that normally favor ?4-?4 CP formation. Further, we demonstrate that ?1 is stoichiometrically limiting for ?-ring assembly, and that enhancing ?1 levels is sufficient to increase proteasome abundance and enhance stress tolerance in yeast. Together, our data indicate that the abundance of ?1 exerts multiple impacts on proteasome assembly and composition, and we propose that the limited ?1 levels observed in yeast may prime cells for alternative proteasome assembly following environmental stimuli.

SUBMITTER: Howell LA 

PROVIDER: S-EPMC6712033 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature