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Cited by 15Cancer-related Molecular PathwaysNuclear Structure and FunctionRNA and protein synthesis mechanisms

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SURF2 is a MDM2 antagonist in triggering the nucleolar stress response

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Tagnères, Sophie, Santo, Paulo Espirito, Radermecker, Julie, Rinaldi, Dana, Froment, Carine, Provost, Quentin, Bongers, Manon, Capeille, Solemne, Watkins, Nick, Marcoux, Julien, Gleizes, Pierre-Emmanuel, Marcel, Virginie, Plisson-Chastang, Célia, Lebaron, Simon·2024·Nature Communications
DOI 10.1038/s41467-024-52659-xPMC PMC11436901

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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.

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Metadata

Authors
Tagnères, S., Santo, P. E., Radermecker, J., Rinaldi, D., Froment, C., Provost, Q., Bongers, M., Capeille, S., Watkins, N., Marcoux, J., Gleizes, P.-E., Marcel, V., Plisson-Chastang, C., & Lebaron, S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Lyon 1 Université (FR)
  • Newcastle University (GB)
Corresponding author
Lebaron, Simon
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-09-27
Volume
15
Issue
1
Pages
8404-8404
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-52659-x
PMC
PMC11436901
OpenAlex
W4402903566
Cited by
15
References
3
Citations by year
2026: 6 · 2025: 9
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ligue Contre le Cancer (62339, Labelisation)
  • Institut National Du Cancer (PLBIO022-065)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
nucleolar stress response, ribosome biogenesis, p53 stabilization, tumor resistance, adrenocortical carcinoma, prognostic factors, chemoresistance
MeSH terms
RNA-Seq, Antineoplastic Agents, Cell Nucleolus, Cell Survival, Humans, Neoplasms, Proteins, Ribonucleoproteins, Ribosomes, Stress, Physiological, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-mdm2, Protein Stability

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