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

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, Georg Tascher, Katherine E. Bohnsack and Stefan Müller ()
Additional contact information
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
Tanja Piller: Goethe University Frankfurt, Medical Faculty
Soraya Hölper: Goethe University Frankfurt, Medical Faculty
Sara Uhan: Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Manuel Kaulich: Goethe University Frankfurt, Medical Faculty
Matthias Wirth: Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Ulrich Keller: Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Georg Tascher: Goethe University Frankfurt, Medical Faculty
Katherine E. Bohnsack: University Medical Centre Göttingen
Stefan Müller: Goethe University Frankfurt, Medical Faculty

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43751-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43751-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43751-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().