ArticleNucleic acids research2024
The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- Points of Departure for BPDE-induced cellular senescence and cell death are characterized by altered DNA damage signaling and regulated by unrepaired DNA double-strand breaks.Archives of toxicology · 2026Article
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Self-Assembling Hybrid Hydrogel Reprograms the Stromal Vascular Fraction to Treat Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overview of molecular signatures of senescence and associated resources: pros and cons.FEBS open bio · 2026Review
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Evaluation of statistical differential analysis methods for identification of senescent cells using single-cell transcriptomics.Cell reports methods · 2026Article
- Senotherapeutics in Malignant Brain Cancer Therapy.Current oncology reports · 2025Review
- Oxidative Stress, Inflammation, and Cellular Senescence in Neuropathic Pain: Mechanistic Crosstalk.Antioxidants (Basel, Switzerland) · 2025Review
- Pleiotropic Effects of Metformin on the Chemotherapy Response of HPV-Positive Cancer Cells.Journal of medical virology · 2025Article
- Therapy-induced senescence of glioblastoma cells is determined by the p21Cell death & disease · 2025Article
- Overexpression of βTrCP1 elicits cell death in cisplatin-induced senescent cells.Cell death & disease · 2025Article
- Emerging Role of the DREAM Complex in Cancer and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- PIM1 induces hypoxia-related fibroblast senescence in a mouse model of stress urinary incontinence.PloS one · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Cellular senescence, a major driver of aging, can be stimulated by DNA damage, and is counteracted by the DNA repair machinery. Here we show that in p16INK4a-deficient cells, senescence induction by the environmental genotoxin B[a]P or ionizing radiation (IR) completely depends on p21CIP1. Immunoprecipitation-based mass spectrometry interactomics data revealed that during senescence induction and maintenance, p21CIP1 specifically inhibits CDK4 and thereby activates the DREAM complex. Genome-wide transcriptomics revealed striking similarities in the response induced by B[a]P and IR. Among the top 100 repressed genes 78 were identical between B[a]P and IR and 76 were DREAM targets. The DREAM complex transcriptionally silences the main proliferation-associated transcription factors E2F1, FOXM1 and B-Myb as well as multiple DNA repair factors. Knockdown of p21CIP1, E2F4 or E2F5 diminished both, repression of these factors and senescence. The transcriptional profiles evoked by B[a]P and IR largely overlapped with the profile induced by pharmacological CDK4 inhibition, further illustrating the role of CDK4 inhibition in genotoxic stress-induced senescence. Moreover, data obtained by live-cell time-lapse microscopy suggest the inhibition of CDK4 by p21CIP1 is especially important for arresting cells which slip through mitosis. Overall, we identified the p21CIP1/CDK4/DREAM axis as a master regulator of genotoxic stress-induced senescence.
Indexed as
Identifiers
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.