SURF2 is a MDM2 antagonist in triggering the nucleolar stress response.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 21 11 2023
accepted: 16 09 2024
medline: 28 9 2024
pubmed: 28 9 2024
entrez: 27 9 2024
Statut: epublish

Résumé

Cancer cells rely on high ribosome production to sustain their proliferation rate. Many chemotherapies impede ribosome production which is perceived by cells as "nucleolar stress" (NS), triggering p53-dependent and independent pathways leading to cell cycle arrest and/or apoptosis. The 5S ribonucleoprotein (RNP) particle, a sub-ribosomal particle, is instrumental to NS response. Upon ribosome assembly defects, the 5S RNP accumulates as free form. This free form is able to sequester and inhibit MDM2, thus promoting p53 stabilization. To investigate how cancer cells can resist to NS, here we purify free 5S RNP and uncover an interaction partner, SURF2. Functional characterization of SURF2 shows that its depletion increases cellular sensitivity to NS, while its overexpression promotes their resistance to it. Consistently, SURF2 is overexpressed in many cancers and its expression level is an independent marker of prognosis for adrenocortical cancer. Our data demonstrate that SURF2 buffers free 5S RNP particles, and can modulate their activity, paving the way for the research of new molecules that can finely tune the response to nucleolar stress in the framework of cancer therapies.

Identifiants

pubmed: 39333141
doi: 10.1038/s41467-024-52659-x
pii: 10.1038/s41467-024-52659-x
doi:

Substances chimiques

Proto-Oncogene Proteins c-mdm2 EC 2.3.2.27
MDM2 protein, human EC 2.3.2.27
Tumor Suppressor Protein p53 0
TP53 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8404

Subventions

Organisme : Ligue Contre le Cancer
ID : 62339
Organisme : Ligue Contre le Cancer
ID : Labelisation
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : PLBIO022-065

Informations de copyright

© 2024. The Author(s).

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Auteurs

Sophie Tagnères (S)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Paulo Espirito Santo (PE)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Julie Radermecker (J)

Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, CEDEX 08, Lyon, France.

Dana Rinaldi (D)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Carine Froment (C)

Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Infrastructure Nationale de Protéomique, ProFI, Toulouse, France.

Quentin Provost (Q)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Manon Bongers (M)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Solemne Capeille (S)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Nick Watkins (N)

Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK.

Julien Marcoux (J)

Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III-Paul Sabatier (UPS), Toulouse, France.
Infrastructure Nationale de Protéomique, ProFI, Toulouse, France.

Pierre-Emmanuel Gleizes (PE)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Virginie Marcel (V)

Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, CEDEX 08, Lyon, France.

Célia Plisson-Chastang (C)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France.

Simon Lebaron (S)

Molecular, Cellular and Developmental Biology unit (MCD), Centre de Biologie Integrative (CBI), Team with an accreditation from the French "Ligue contre le Cancer" organism., University of Toulouse, CNRS, UPS, 118 route de Narbonne, Toulouse, Cedex, France. simon.lebaron@univ-tlse3.fr.
Institut national de la santé et de la recherche médicale (INSERM), Paris, France. simon.lebaron@univ-tlse3.fr.

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