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Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis

Author

Listed:
  • Judith Dönig

    (Goethe University Frankfurt, Medical Faculty)

  • Hannah Mende

    (Goethe University Frankfurt, Medical Faculty)

  • Jimena Davila Gallesio

    (University Medical Centre Göttingen)

  • Kristina Wagner

    (Goethe University Frankfurt, Medical Faculty)

  • Paul Hotz

    (Goethe University Frankfurt, Medical Faculty)

  • Kathrin Schunck

    (Goethe University Frankfurt, Medical Faculty
    PharmBioTec gGmbH)

  • Tanja Piller

    (Goethe University Frankfurt, Medical Faculty
    Sanofi AG)

  • Soraya Hölper

    (Goethe University Frankfurt, Medical Faculty
    Sanofi AG)

  • Sara Uhan

    (Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    German Cancer Consortium (DKTK)
    Max Delbrück Center)

  • Manuel Kaulich

    (Goethe University Frankfurt, Medical Faculty)

  • Matthias Wirth

    (Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    German Cancer Consortium (DKTK)
    Max Delbrück Center
    University Medical Center Göttingen)

  • Ulrich Keller

    (Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    German Cancer Consortium (DKTK)
    Max Delbrück Center)

  • Georg Tascher

    (Goethe University Frankfurt, Medical Faculty)

  • Katherine E. Bohnsack

    (University Medical Centre Göttingen)

  • Stefan Müller

    (Goethe University Frankfurt, Medical Faculty
    German Cancer Consortium (DKTK))

Abstract

Ribosome biogenesis is a multi-step process, in which a network of trans-acting factors ensures the coordinated assembly of pre-ribosomal particles in order to generate functional ribosomes. Ribosome biogenesis is tightly coordinated with cell proliferation and its perturbation activates a p53-dependent cell-cycle checkpoint. How p53-independent signalling networks connect impaired ribosome biogenesis to the cell-cycle machinery has remained largely enigmatic. We demonstrate that inactivation of the nucleolar SUMO isopeptidases SENP3 and SENP5 disturbs distinct steps of 40S and 60S ribosomal subunit assembly pathways, thereby triggering the canonical p53-dependent impaired ribosome biogenesis checkpoint. However, inactivation of SENP3 or SENP5 also induces a p53-independent checkpoint that converges on the specific downregulation of the key cell-cycle regulator CDK6. We further reveal that impaired ribosome biogenesis generally triggers the downregulation of CDK6, independent of the cellular p53 status. Altogether, these data define the role of SUMO signalling in ribosome biogenesis and unveil a p53-independent checkpoint of impaired ribosome biogenesis.

Suggested Citation

  • Judith Dönig & Hannah Mende & Jimena Davila Gallesio & Kristina Wagner & Paul Hotz & Kathrin Schunck & Tanja Piller & Soraya Hölper & Sara Uhan & Manuel Kaulich & Matthias Wirth & Ulrich Keller & Geor, 2023. "Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43751-9
    DOI: 10.1038/s41467-023-43751-9
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    References listed on IDEAS

    as
    1. Emilien Nicolas & Pascaline Parisot & Celina Pinto-Monteiro & Roxane de Walque & Christophe De Vleeschouwer & Denis L. J. Lafontaine, 2016. "Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    2. Heeseon An & Alban Ordureau & Maria Körner & Joao A. Paulo & J. Wade Harper, 2020. "Systematic quantitative analysis of ribosome inventory during nutrient stress," Nature, Nature, vol. 583(7815), pages 303-309, July.
    3. Jacob Gordon & Fleur L. Chapus & Elizabeth G. Viverette & Jason G. Williams & Leesa J. Deterding & Juno M. Krahn & Mario J. Borgnia & Joseph Rodriguez & Alan J. Warren & Robin E. Stanley, 2022. "Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Lisa Fromm & Sebastian Falk & Dirk Flemming & Jan Michael Schuller & Matthias Thoms & Elena Conti & Ed Hurt, 2017. "Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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