ArticleGenes & development2017
The PIDDosome activates p53 in response to supernumerary centrosomes.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed.
- Comparative insights into the apoptosome, inflammasomes and PIDDosome.Nature reviews. Immunology · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- PIDDosome deficiency impairs bone remodeling by increasing osteoclast ploidy and function.Cell death and differentiation · 2026Article
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- The immediate cellular response to whole-genome doubling is conserved across polyploid contexts.bioRxiv : the preprint server for biology · 2026Article
- Reciprocal compensation of caspase-2 and p53 regulates the DNA damage response in HCT116 colon cancer cells.The Journal of biological chemistry · 2026Article
- Sensing centrosome amplification: the interface between centriole duplication and autophagy.Nature communications · 2026Article
- The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity.Nature communications · 2026Article
- The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development.Cell death and differentiation · 2026Article
- PARP4 ADP-ribosylates PIDD1 to complete a phospho/SUMO/PAR-ylation cascade that orchestrates PIDDosome assembly.Science advances · 2026Article
- Sister chromatid separation determines the proliferative properties upon whole-genome duplication via homologous chromosome arrangement.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- AML Disparities Across Racial Ancestry Groups: A Spotlight on the NPM1 Mutations.International journal of molecular sciences · 2026Review
- Caspase-2 deficiency drives pathogenic liver polyploidy and increases age-associated hepatocellular carcinoma in mice.Science advances · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- Cell Fusion-Mediated Induction of Polyploidy, Aneuploidy, and Genomic Instability in Cancer Cells.Advances in experimental medicine and biology · 2026Review
- Biological clocks keep a watch on mitosis.Nature cell biology · 2026Review
- Genomic Reshuffling After Cell Fusion: Catalyst for Cancer Evolution and Progression.Advances in experimental medicine and biology · 2026Review
- The Centriole Biogenesis Cycle: Temporal Mechanisms, Autonomy and Coupling to the Cell Cycle and Other Cellular Clocks.Advances in experimental medicine and biology · 2026Review
- Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.Cell proliferation · 2025Article
- The Impact of Polyploid Giant Cancer Cells: The Root of Stress Resilience.Cancer science · 2025Review
90 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest. This pathway also restrains the extent of developmentally scheduled polyploidization by regulating p53 levels in hepatocytes during liver organogenesis. Taken together, the PIDDosome acts as a first barrier, engaging p53 to halt the proliferation of cells carrying more than one mature centrosome to maintain genome integrity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.