Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.
Amino Acids
/ metabolism
Animals
Apoptosis
/ physiology
Autoantigens
Cell Line, Tumor
Cell Nucleus
/ metabolism
DNA Repair Enzymes
/ metabolism
DNA-Binding Proteins
/ metabolism
Eukaryotic Cells
Exercise
Fibroblasts
Humans
Mice
Nutrients
Proteasome Endopeptidase Complex
/ metabolism
Protein Biosynthesis
Proteolysis
Starvation
Stress, Physiological
Ubiquitin
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 11 2021
30 11 2021
Historique:
received:
23
12
2019
accepted:
09
11
2021
entrez:
1
12
2021
pubmed:
2
12
2021
medline:
4
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34848715
doi: 10.1038/s41467-021-27306-4
pii: 10.1038/s41467-021-27306-4
pmc: PMC8633328
doi:
Substances chimiques
Amino Acids
0
Autoantigens
0
DNA-Binding Proteins
0
Ki antigen
0
RAD23B protein, human
0
Ubiquitin
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6984Subventions
Organisme : CIHR
ID : MOP159539
Pays : Canada
Organisme : CIHR
ID : GER-163050
Pays : Canada
Organisme : CIHR
ID : MOP126009
Pays : Canada
Informations de copyright
© 2021. The Author(s).
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