ArticleOncogene2005
Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 266 citations in OpenAlex.
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- Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.Blood advances · 2026Article
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma.PloS one · 2026Article
- Low hyper-oxygen exposure induces p21-dependent p53-independent senescence in alveolar cells.International journal of medical sciences · 2026Article
- Profiling the Preclinical Pharmacokinetics and Biodistribution of a Platinum(IV)-Based Oxaliplatin Prodrug OxaliTEX and Their Significance to Antitumor Response.Molecular pharmaceutics · 2025Article
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- Editorial Expression of Concern: Upregulation of p27 and its inhibition of CDK2/cyclin E activity following DNA damage by a novel platinum agent are dependent on the expression of p21.British journal of cancer · 2025Article
- Clusterin Deficiency Promotes Cellular Senescence in Human Astrocytes.Molecular neurobiology · 2025Article
- YK-4-279 Induces Osteosarcoma Cell Cycle Arrest, DNA Damage Response, and Apoptosis by Regulating the MAPK Cascade.Drug design, development and therapy · 2025Article
- NUPR1 contributes to endocrine therapy resistance by modulating BIRC5 expression and inducing luminal B-ERBB2Journal of Cancer · 2025Article
- Cellular zinc status alters chromatin accessibility and binding of p53 to DNA.Life science alliance · 2024Article
- Review
- The oscillation of mitotic kinase governs cell cycle latches in mammalian cells.Journal of cell science · 2024Article
- Bone metastasis in non-small-cell lung cancer: genomic characterization and exploration of potential targets.Therapeutic advances in medical oncology · 2024Article
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
- Cellular zinc status alters chromatin accessibility and binding of transcription factor p53 to genomic sites.bioRxiv : the preprint server for biology · 2023Article
- RYBP contributes to improved prognosis in colorectal cancer via regulation of cell cycle, apoptosis and oxaliplatin sensitivity.International journal of oncology · 2023Article
- Cellular senescence in glioma.Journal of neuro-oncology · 2023Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
DNA damage often activates the p53-p21 pathway and causes G(1)-phase arrest in mammalian cells. Although there is ample evidence that p21 induction by p53 leads to Cdk2 inhibition, it is unclear whether this checkpoint event also leads to Cdk4 inhibition. Diaminocyclohexane(trans-diacetato)(dichloro) platinum(IV) (DAP), a platinum-based coordination complex, is a DNA-damaging agent that is effective against a variety of tumor cells resistant to the parental drug cisplatin. Our previous studies established that treatment of human cancer cells with low effective concentrations of DAP specifically activates the G(1)-phase checkpoint and simultaneously inhibit Cdk4 and Cdk2 activities. Here we demonstrate that DAP treatment of human cancer cells activates the p53-p21 pathway without activating other known mechanisms that inhibit Cdk4 and Cdk2 activities. The induced p21 binds to both the Cdk4/cyclin D and Cdk2/cyclin E complexes and inhibits both of their kinase activities. Conversely, inhibition of p21 induction by cycloheximide or by p21 gene deletion prevents DAP-induced inhibition of Cdk4 and Cdk2 activities. Attenuated p53 expression and p21 induction also eliminates DAP-induced G(1)-phase arrest and inhibition of Cdk4 and Cdk2 activities. Together, these findings establish that activation of the p53-p21 pathway is responsible for the DAP-induced G(1)-phase checkpoint response and provide the first solid evidence that p21 induction by p53 during a DNA damage-induced G(1)-phase checkpoint response inhibits both Cdk4 and Cdk2 activities.
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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.