2026-04-13T04:12:13Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2092452025-12-05T12:40:56Zcom_2072_1057col_2072_478916col_2072_478917

urn:hdl:2445/209245 AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans Pispa, Johanna Mikkonen, Elisa Arpalahti, Leena Jin, Congyu Martínez Fernández, Carmen Cerón Madrigal, Julián Holmberg, Carina I. Proteïnes Homeòstasi Proteins Homeostasis 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. 2024-03-26T19:36:36Z 2024-03-26T19:36:36Z 2023-10-01 2023-11-22T08:57:16Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1016/j.isci.2023.107886 iScience, 2023, vol. 26, num. 10 https://doi.org/10.1016/j.isci.2023.107886 cc by (c) Pispa, Johanna et al., 2023 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Elsevier BV Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))