AKIR-1 regulates proteasome subcellular function in .

Polyubiquitinated proteins are primarily degraded by the ubiquitin-proteasome system (UPS). Proteasomes are present both in the cytoplasm and nucleus. Here, we investigated mechanisms coordinating proteasome subcellular localization and activity in a multicellular organism. We identified the nuclear protein-encoding gene as a proteasome regulator in a genome-wide RNAi screen. We demonstrate that depletion of causes nuclear accumulation of endogenous polyubiquitinated proteins in intestinal cells, concomitant with slower proteasomal degradation in this subcellular compartment. Remarkably, is essential for nuclear localization of proteasomes both in oocytes and intestinal cells but affects differentially the subcellular distribution of polyubiquitinated proteins. We further reveal that importin genetically interacts with and influences nuclear localization of a polyubiquitin-binding reporter. Our study shows that the conserved AKIR-1 is an important regulator of the subcellular function of proteasomes in a multicellular organism, suggesting a role for AKIR-1 in proteostasis maintenance.