SURF2 is a MDM2 antagonist in triggering the nucleolar stress response

Sophie Tagnères, Paulo Espirito Santo, Julie Radermecker, Dana Rinaldi, Carine Froment, Quentin Provost, Manon Bongers, Solemne Capeille, Nick Watkins, Julien Marcoux, Pierre-Emmanuel Gleizes, Virginie Marcel, Célia Plisson-Chastang and Simon Lebaron ()
Additional contact information
Sophie Tagnères: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Paulo Espirito Santo: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Julie Radermecker: CEDEX 08
Dana Rinaldi: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Carine Froment: Université Toulouse III-Paul Sabatier (UPS)
Quentin Provost: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Manon Bongers: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Solemne Capeille: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Nick Watkins: Newcastle University
Julien Marcoux: Université Toulouse III-Paul Sabatier (UPS)
Pierre-Emmanuel Gleizes: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Virginie Marcel: CEDEX 08
Célia Plisson-Chastang: University of Toulouse, CNRS, UPS, 118 route de Narbonne
Simon Lebaron: University of Toulouse, CNRS, UPS, 118 route de Narbonne

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-52659-x

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