ArticleNature cell biology2016
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
200 citing papers in PubMed, 306 citations in OpenAlex.
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- PP4 deficiency drives airway epithelial senescence via the PERK-eIF2α-ATF4-p21 axis in severe asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Ubiquitin-dependent degradation of p27Kip1 and p21Waf1/Cip1 by AMBRA1 ensures G1 and S phase progression and limits replication stress.Nucleic acids research · 2026Article
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Pre-Encoded IFN-I Sensitivity Exacerbates Memory T Cell Senescence in Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- Overview of molecular signatures of senescence and associated resources: pros and cons.FEBS open bio · 2026Review
- EYA4 promotes cellular senescence by enhancing P21 transcription through interaction with SIX2.Advanced biotechnology · 2026Article
- The p21 resilience network: a conceptual framework linking senescence to ferroptosis and cuproptosis resistance.NPJ systems biology and applications · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication.Nature communications · 2026Article
- BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53.BMC biology · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Article
- Immune cell senescence drives responsiveness to immunotherapy in melanoma.Molecular cancer · 2025Article
- Article
- Irradiated obese adipocytes are prone to oxidative stress, inflammation, senescence, and fibrosis.Scientific reports · 2025Article
140 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 13 institutions in 8 countries.
Funding
Abstract
The cyclin-dependent kinase inhibitor p21(WAF1/CIP1) (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4-CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery-an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs.
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What OpenQuestion holds
Registered trials
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.