ArticleCell reports2022
Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 51 citations in OpenAlex.
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- Elucidating structure-function relationships in the mammalian nucleolus.Nature reviews. Molecular cell biology · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Reversible Nucleolar Stress and Cell Growth Arrest Triggered by Acidic pH.Journal of cellular physiology · 2026Article
- RNA Pol I shapes meiotic chromatin, germline H3K4me3 dynamics, and oogenesis independent of ribosome assembly.Cell reports · 2026Article
- Loss of p53 Provokes NF-κB-Dependent Disruption of Nucleolar Cap and Nucleoplasmic Redistribution of Fibrillarin During Nucleolar Stress.Biomolecules · 2026Article
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- Lessons in longevity from blood stem cells under protein stress.Trends in cell biology · 2026Review
- Establishment of an imaging-based screening pipeline for the identification of human ribosome biogenesis inhibitors.BMC biology · 2025Article
- Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2025Review
- G9a controls plasma cell differentiation through FOXO1 and ETS1 binding site regulatory networks.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The Role of Translation-Associated Proteins in p53 Modulation: Mechanisms and Implications.International journal of molecular sciences · 2025Review
- RNA Pol I activity is required for meiotic chromatin organization and the H3K4me3 gradient essential for oogenesis, independent of ribosome synthesis.bioRxiv : the preprint server for biology · 2025Article
- Review
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- HEATR3 recognizes membrane rupture and facilitates xenophagy in response toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ribosome-directed cancer therapies: the tip of the iceberg?Trends in pharmacological sciences · 2025Review
- A role for the kinetochore protein, NUF2, in ribosome biogenesis.Molecular biology of the cell · 2025Article
- SURF2 is a MDM2 antagonist in triggering the nucleolar stress response.Nature communications · 2024Article
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Authors and funding
32 authors at 8 institutions in 5 countries.
Katherine M HannanACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; Division of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
Priscilla SooACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Mei S WongACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; Division of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia.
Justine K LeeInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle-Upon-Tyne, UK.
Nadine HeinACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Perlita PohACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Kira D WysokeACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Tobias D WilliamsACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Christian MontelleseDepartment of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Lorey K SmithDivision of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Sheren J Al-ObaidiACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Lorena Núñez-VillacísACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Megan PavyACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Jin-Shu HeANU Centre for Therapeutic Discovery, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Kate M ParsonsANU Centre for Therapeutic Discovery, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Karagh E LoringACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Tess MorrisonACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Jeannine DieschDivision of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Gaetan BurgioACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Rita FerreiraACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Zhi-Ping FengThe John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Cathryn M GouldDivision of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Piyush B MadhamshettiwarDivision of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Johan FlygareLund Stem Cell Center, Lund University, BMC A12, Lund, Sweden.
Thomas J GondaSchool of Pharmacy, University of Queensland, Brisbane, QLD 4102, Australia.
Kaylene J SimpsonDivision of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Ulrike KutayDepartment of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Richard B PearsonACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; Division of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Christoph EngelRegensburg Center for Biochemistry, University of Regensburg, 93053 Regensburg, Germany.
Nicholas J WatkinsInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle-Upon-Tyne, UK.
Ross D HannanACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; Division of Research, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4067, Australia. Electronic address: ross.hannan@anu.edu.au.
Amee J GeorgeACRF Department of Cancer Biology and Therapeutics and Division of Genome Sciences and Cancer, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; ANU Centre for Therapeutic Discovery, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia; Department of Clinical Pathology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: amee.george@anu.edu.au.
Australian National University · AUPeter MacCallum Cancer Centre · AUETH Zurich · CHNewcastle University · GBLund University · SEThe University of Melbourne · AUThe University of Queensland · AUUniversity of Regensburg · DE
Funding
Biotechnology and Biological Sciences Research Council BB/R00143X/1
Abstract
The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
Indexed as
Proto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53Cell NucleolusRibosomal ProteinsSignal TransductionProto-Oncogene Proteins c-mdm2Ribosomal ProteinsTumor Suppressor Protein p53CP: Molecular biologyhigh-content screeninghigh-throughput screeningnucleolar surveillance pathwaynucleolusp53ribosomal proteinsribosome biogenesisstress
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