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Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.

ABSTRACT: Eukaryotic 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.

SUBMITTER: Uriarte M

PROVIDER: S-EPMC8633328 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.

Uriarte Maxime M Sen Nkwe Nadine N Tremblay Roch R Ahmed Oumaima O Messmer Clémence C Mashtalir Nazar N Barbour Haithem H Masclef Louis L Voide Marion M Viallard Claire C Daou Salima S Abdelhadi Djaileb D Ronato Daryl D Paydar Mohammadjavad M Darracq Anaïs A Boulay Karine K Desjardins-Lecavalier Nicolas N Sapieha Przemyslaw P Masson Jean-Yves JY Sergeev Mikhail M Kwok Benjamin H BH Hulea Laura L Mallette Frédérick A FA Milot Eric E Larrivée Bruno B Wurtele Hugo H Affar El Bachir EB

Nature communications 20211130 1

Eukaryotic 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 (Starva ...[more]

PMID: 34848715

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Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.

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Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.

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