Authors

Maxime Uriarte,1,2 Nadine Sen Nkwe,2,3 Roch Tremblay,2,3 Oumaima Ahmed,2,3 Clémence Messmer,1,2 Nazar Mashtalir,4,5 Haithem Barbour,2,6 Louis Masclef,1,2 Marion Voide,2,3 Claire Viallard,2,7 Salima Daou,8 Djaileb Abdelhadi,1,2 Daryl Ronato,9,10 Mohammadjavad Paydar,11 Anaïs Darracq,2,3 Karine Boulay,2,7 Nicolas Desjardins-Lecavalier,2 Przemyslaw Sapieha,2,12,13 Jean-Yves Masson,9,10 Mikhail Sergeev,2,7 Benjamin H. Kwok,7,11 Laura Hulea,2,7 Frédérick A. Mallette,2,7 Eric Milot,2,7 Bruno Larrivée,2,7 Hugo Wurtele,2,7 and El Bachir Affarcorresponding author2,7

Affiliations

"1Department of Biochemistry and Molecular Medicine, University of Montréal, H3C 3J7 Montreal, QC Canada
2Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4 Canada
3Molecular Biology Programs, University of Montreal, Montréal, H3A 0G4 QC Canada
4Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215 USA
5Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA
6Biomedical Sciences Programs, University of Montréal, Montréal, H3C 3T5 QC Canada
7Department of Medicine, University of Montréal, Montréal, H3C 3J7 QC Canada
8Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5 Canada
9CHU de Québec Research Center, Oncology Division, 9 McMahon, Québec City, QC G1R 3S3 Canada
10Laval University Cancer Research Center, Québec City, QC G1V 0A6 Canada
11Institute for Research in Immunology and Cancer (IRIC), University of Montréal, Montréal, QC H3T 1J4 Canada
12Department of Ophthalmology, University of Montréal, Montréal, QC Canada
13Department of Neurology-Neurosurgery, McGill University, Montréal, QC Canada
El Bachir Affar, Email: [email protected]
corresponding authorCorresponding author."

Topic

Cell Biology, Medical Research

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.

Subject terms: Apoptosis, Nutrient signalling

DOI: https://dx.doi.org/ 10.1038/s41467-021-27306-4

Extract

Brightfield (DIC) and EPI-fluorescence images were collected using a Zeiss Plan-Apochromat ×63/1.4 NA oil immersion objective lens. GFP was excited with a CoolLED pE-300 lite

Product Associated Features

CoolLED’s pE-300lite is a simple white light LED illumination system that offers intense, broad-spectrum LED illumination for fluorescence microscopy. The system is perfect for hospital and regular research laboratory environments and is affordable within consumables budgets.

Product Type

pE-300lite

Journal

Nature Communications

Year of Publication

2021

Country of Publication

UK