Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43751-9 |
| _version_ | 1797397863151435776 |
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| author | 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 Stefan Müller |
| author_facet | 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 Stefan Müller |
| author_sort | Judith Dönig |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:17:21Z |
| format | Article |
| id | doaj.art-2edd2d3bfab1439685a793e49a34886e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:17:21Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2edd2d3bfab1439685a793e49a34886e2023-12-10T12:23:20ZengNature PortfolioNature Communications2041-17232023-12-0114112010.1038/s41467-023-43751-9Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesisJudith Dönig0Hannah Mende1Jimena Davila Gallesio2Kristina Wagner3Paul Hotz4Kathrin Schunck5Tanja Piller6Soraya Hölper7Sara Uhan8Manuel Kaulich9Matthias Wirth10Ulrich Keller11Georg Tascher12Katherine E. Bohnsack13Stefan Müller14Institute of Biochemistry II, Goethe University Frankfurt, Medical FacultyInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyDepartment of Molecular Biology, University Medical Centre GöttingenInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyDepartment of Hematology, Oncology and Cancer Immunology (Campus Benjamin Franklin), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyDepartment of Hematology, Oncology and Cancer Immunology (Campus Benjamin Franklin), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Hematology, Oncology and Cancer Immunology (Campus Benjamin Franklin), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyDepartment of Molecular Biology, University Medical Centre GöttingenInstitute of Biochemistry II, Goethe University Frankfurt, Medical FacultyAbstract 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.https://doi.org/10.1038/s41467-023-43751-9 |
| spellingShingle | 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 Stefan Müller Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis Nature Communications |
| title | Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis |
| title_full | Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis |
| title_fullStr | Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis |
| title_full_unstemmed | Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis |
| title_short | Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis |
| title_sort | characterization of nucleolar sumo isopeptidases unveils a general p53 independent checkpoint of impaired ribosome biogenesis |
| url | https://doi.org/10.1038/s41467-023-43751-9 |
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