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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 akir-1 as a proteasome regulator in a genome-wide Caenorhabditis elegans RNAi screen. We demonstrate that depletion of akir-1 causes nuclear accumulation of endogenous polyubiquitinated proteins in intestinal cells, concomitant with slower in vivo proteasomal degradation in this subcellular compartment. Remarkably, akir-1 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 ima-3 genetically interacts with akir-1 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.
Pubmed ID: 37767001
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Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
View all literature mentionsCaenorhabditis elegans with name C. elegans wild type (ancestral). from WB.
View all literature mentionsThis unknown targets Mouse IgM, H & L Chain
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Proteasome 20S α12356& 7 subunits mAb (MCP231)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgM (Heavy chain)
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsCaenorhabditis elegans with name EMPTY from WB.
View all literature mentionsCaenorhabditis elegans with name EMPTY from WB.
View all literature mentionsCaenorhabditis elegans with name E01A2.6(gk528) I. from WB.
View all literature mentionsCaenorhabditis elegans with name EMPTY from WB.
View all literature mentionsCaenorhabditis elegans with name rrf-3(pk1426) II. from WB.
View all literature mentionsCaenorhabditis elegans with name EMPTY from WB.
View all literature mentionsCaenorhabditis elegans with name EMPTY from WB.
View all literature mentionsCaenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.
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