AKIR-1 Regulates Proteasome Localization and Function in Caenorhabditis elegans

Abstract

Regulated protein clearance is vital for cells to maintain protein homeostasis and the conditions essential for survival. The primary machinery for intracellular protein degradation is the ubiquitin- proteasome system (UPS), by which ubiquitin-tagged proteins are degraded by the proteasome. Proteasomes are present both in the cytoplasm and the nucleus, but the mechanisms coordinating proteasome activity and its subcellular localization in a multicellular organism are still unclear. Here, we identified the nuclear protein-encoding gene akir-1 as a proteasome regulator in a genome-wide Caenorhabditis elegans (C. elegans) RNAi screen. We show that the depletion of akir-1 causes accumulation of endogenous polyubiquitinated proteins in the nuclei of intestinal cells, concomitant with slower in vivo proteasomal degradation in this subcellular compartment. Remarkably, the loss of akir-1 does not induce an accumulation of polyubiquitinated proteins in oocyte nuclei, though akir-1 is essential for the nuclear localization of proteasomes in both cell types. We further show that the importin family member ima-3 genetically interacts with akir-1, and affects subcellular distribution of polyubiquitinated proteins in intestinal cells. We show for the first time that conserved AKIR-1 is important for the nuclear transport of proteasomes in a multicellular organism, suggesting a role for AKIR-1 in the maintenance of proteostasis.