AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans

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...

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Autores: Pispa, Johanna, Mikkonen, Elisa, Arpalahti, Leena, Jin, Congyu, Martínez Fernández, Carmen, Cerón Madrigal, Julián, Holmberg, Carina I.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/209245
Acceso en línea:https://hdl.handle.net/2445/209245
Access Level:acceso abierto
Palabra clave:Proteïnes
Homeòstasi
Proteins
Homeostasis
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spelling AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegansPispa, JohannaMikkonen, ElisaArpalahti, LeenaJin, CongyuMartínez Fernández, CarmenCerón Madrigal, JuliánHolmberg, Carina I.ProteïnesHomeòstasiProteinsHomeostasisPolyubiquitinated 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.Elsevier BV2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/209245Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.isci.2023.107886iScience, 2023, vol. 26, num. 10https://doi.org/10.1016/j.isci.2023.107886cc by (c) Pispa, Johanna et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2092452026-05-27T06:46:51Z
dc.title.none.fl_str_mv AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
title AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
spellingShingle AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
Pispa, Johanna
Proteïnes
Homeòstasi
Proteins
Homeostasis
title_short AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
title_full AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
title_fullStr AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
title_full_unstemmed AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
title_sort AKIR-1 regulates proteasome subcellular function in Caenorhabditis elegans
dc.creator.none.fl_str_mv Pispa, Johanna
Mikkonen, Elisa
Arpalahti, Leena
Jin, Congyu
Martínez Fernández, Carmen
Cerón Madrigal, Julián
Holmberg, Carina I.
author Pispa, Johanna
author_facet Pispa, Johanna
Mikkonen, Elisa
Arpalahti, Leena
Jin, Congyu
Martínez Fernández, Carmen
Cerón Madrigal, Julián
Holmberg, Carina I.
author_role author
author2 Mikkonen, Elisa
Arpalahti, Leena
Jin, Congyu
Martínez Fernández, Carmen
Cerón Madrigal, Julián
Holmberg, Carina I.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes
Homeòstasi
Proteins
Homeostasis
topic Proteïnes
Homeòstasi
Proteins
Homeostasis
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/209245
url https://hdl.handle.net/2445/209245
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv 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
dc.rights.none.fl_str_mv cc by (c) Pispa, Johanna et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Pispa, Johanna et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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