ArticleBritish journal of cancer2006
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.
Article in British journal of cancer, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 27 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
27 citing papers in PubMed, 44 citations in OpenAlex.
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
- Profiling the Preclinical Pharmacokinetics and Biodistribution of a Platinum(IV)-Based Oxaliplatin Prodrug OxaliTEX and Their Significance to Antitumor Response.Molecular pharmaceutics · 2025Article
- Protective effect of Panax ginseng extract on cisplatin-induced AKI via downregulating cell death associated genes.Scientific reports · 2025Article
- Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking.International journal of molecular sciences · 2021Article
- Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism.Cell death & disease · 2020Article
- Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways.Journal of experimental & clinical cancer research : CR · 2020Article
- Coupling function of cyclin-dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma.Cancer science · 2019Article
- Drug-dependent functionalization of wild-type and mutant p53 in cisplatin-resistant human ovarian tumor cells.Oncotarget · 2017Article
- Evaluation of the cytotoxicity of the Bithionol - cisplatin combination in a panel of human ovarian cancer cell lines.BMC cancer · 2017Article
- Evaluation of the cytotoxicity of the Bithionol-paclitaxel combination in a panel of human ovarian cancer cell lines.PloS one · 2017Article
- Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation.International journal of oncology · 2016Article
- Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma.Scientific reports · 2015Article
- Reactive oxygen species and p21Waf1/Cip1 are both essential for p53-mediated senescence of head and neck cancer cells.Cell death & disease · 2015Article
- MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis by antagonizing CDK2-dependent p27 stability.Oncogene · 2015Article
- Article
- Non-small cell lung cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by telomere overhang oligonucleotides.Cancer letters · 2014Article
- Napsin A as a marker of clear cell ovarian carcinoma.BMC cancer · 2013Article
- Recruitment of trimeric proliferating cell nuclear antigen by G1-phase cyclin-dependent kinases following DNA damage with platinum-based antitumour agents.British journal of cancer · 2013Article
- Mechanism of DNA damage responses induced by exposure to an oligonucleotide homologous to the telomere overhang in melanoma.Oncotarget · 2013Article
- Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma.Cancer science · 2012Article
Corrections and comments
- Expression of concern
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cisplatin analogue 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) (DAP) is a DNA-damaging agent that will be entering clinical trials for its potent cytotoxic effects against cisplatin-resistant tumour cells. This cytotoxicity may reside in its ability to selectively activate G1-phase checkpoint response by inhibiting CDKs via the p53/p21 pathway. We have now evaluated the role of another CDK inhibitor p27 as a contributor to DAP-mediated inhibition of G1-phase CDK2 activity. Our studies in ovarian A2780 tumour cells demonstrate that p27 levels induced by DAP are comparable to or greater than those seen for p21. The induction of p27 is not through a transcriptional mechanism, but rather is due to a four-fold increase in protein stabilisation through a mechanism dependent on p21. Moreover, DAP-induced p21 promoted the selective increase of p27 in the CDK2 complex, but not in CDK4 complex, and this selective increase contributed to inhibition of the CDK2 kinase activity. The inhibited complex contained either p27 or p21, but not both, with the relative levels of cyclin E associated with p27 and p21 indicating that about 25% of the inhibition of CDK2 activity was due to p27 and 75% due to p21. This study provides the first evidence that p27 upregulation is directly attributable to activation of the p53/p21 pathway by a DNA-damaging agent, and promulgates p53/p21/p27 axis as a significant component of checkpoint response.
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.