Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis
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Published:2021-11-30
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Uriarte MaximeORCID, Sen Nkwe Nadine, Tremblay Roch, Ahmed Oumaima, Messmer Clémence, Mashtalir Nazar, Barbour Haithem, Masclef LouisORCID, Voide Marion, Viallard ClaireORCID, Daou Salima, Abdelhadi Djaileb, Ronato DarylORCID, Paydar Mohammadjavad, Darracq Anaïs, Boulay Karine, Desjardins-Lecavalier NicolasORCID, Sapieha PrzemyslawORCID, Masson Jean-YvesORCID, Sergeev Mikhail, Kwok Benjamin H., Hulea Laura, Mallette Frédérick A.ORCID, Milot Eric, Larrivée Bruno, Wurtele Hugo, Affar El BachirORCID
Abstract
AbstractEukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions.
Funder
Gouvernement du Canada | Canadian Institutes of Health Research Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada Cancer Research Society
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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