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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/209245
AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
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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.
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PISPA, Johanna, et al. AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans. iScience. 2023. Vol. 26, num. 10. ISSN 2589-0042. [consulted: 7 of July of 2026]. Available at: https://hdl.handle.net/2445/209245