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

Autor: 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., 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., 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., 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., 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., 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., 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., 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., Watkins N; Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK., 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., 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., 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., 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., 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 27; Vol. 15 (1), pp. 8404. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1038/s41467-024-52659-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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