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

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Item Type:Article
Title:Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis
Creators Name:Dönig, J. and Mende, H. and Davila Gallesio, J. and Wagner, K. and Hotz, P. and Schunck, K. and Piller, T. and Hölper, S. and Uhan, S. and Kaulich, M. and Wirth, M. and Keller, U. and Tascher, G. and Bohnsack, K.E. and Müller, S.
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.
Keywords:Cell Nucleolus, Cell Proliferation, Ribosomal Proteins, Ribosomes, Tumor Suppressor Protein p53
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:8121
Date:8 December 2023
Official Publication:https://doi.org/10.1038/s41467-023-43751-9
PubMed:View item in PubMed

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