SURF2 is a MDM2 antagonist in triggering the nucleolar stress response
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.
Authors
- Quentin Provost
- Célia Plisson‐Chastang (ORCID: https://orcid.org/0000-0002-8439-8428)
- Paulo E. Santo (ORCID: https://orcid.org/0000-0003-4277-3573)
- Pierre‐Emmanuel Gleizes (ORCID: https://orcid.org/0000-0003-0830-7341)
- Simon Lebaron (ORCID: https://orcid.org/0000-0001-7348-2088)
- Julien Marcoux (ORCID: https://orcid.org/0000-0001-7321-7436)
- Virginie Marcel (ORCID: https://orcid.org/0000-0002-9557-8221)
- Carine Froment (ORCID: https://orcid.org/0000-0003-3688-5560)
- Nick Watkins
- Sophie Tagnères
- Julie Radermecker
- Solemne Capeille
- Manon Bongers
- Dana Rinaldi
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut National Polytechnique de Toulouse (FR)
- Centre de Biologie du Développement (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1038/s41467-024-52659-x
- Citations
- 12
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Institute of Cancer Research