ArticleOncogene2001
Activation of p53 by roscovitine-mediated suppression of MDM2 expression.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 119 citations in OpenAlex.
- CDK11 inhibition induces cytoplasmic p21Molecular oncology · 2026Article
- Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα, and cell-cycle signaling in a breast cancer model.Exploration of targeted anti-tumor therapy · 2022Article
- VEGFC/FLT4-induced cell-cycle arrest mediates sprouting and differentiation of venous and lymphatic endothelial cells.Cell reports · 2021Article
- A Different Facet of p53 Function: Regulation of Immunity and Inflammation During Tumor Development.Frontiers in cell and developmental biology · 2021Review
- CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.Cell death & disease · 2020Article
- Targeting the rheumatoid arthritis synovial fibroblast via cyclin dependent kinase inhibition: An early phase trial.Medicine · 2020Article
- Human embryonic stem cells display a pronounced sensitivity to the cyclin dependent kinase inhibitor Roscovitine.BMC molecular and cell biology · 2019Article
- Combined BRD4 and CDK9 inhibition as a new therapeutic approach in malignant rhabdoid tumors.Oncotarget · 2017Article
- p53 dynamics in response to DNA damage vary across cell lines and are shaped by efficiency of DNA repair and activity of the kinase ATM.Science signaling · 2017Article
- Identification of p53-target genes in Danio rerio.Scientific reports · 2016Article
- Selective antitumor activity of roscovitine in head and neck cancer.Oncotarget · 2016Article
- Inhibitors of the p53-Mdm2 interaction increase programmed cell death and produce abnormal phenotypes in the placozoon Trichoplax adhaerens (F.E. Schulze).Development genes and evolution · 2014Article
- Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism.Journal of inflammation (London, England) · 2014Review
- Article
- Implication of transcriptional repression in compound C-induced apoptosis in cancer cells.Cell death & disease · 2013Article
- A fish-specific transposable element shapes the repertoire of p53 target genes in zebrafish.PloS one · 2012Article
- The effect of the combined action of roscovitine and Paclitaxel on the apoptotic and cell cycle regulatory mechanisms in colon and anaplastic thyroid cancer cells.ISRN biochemistry · 2012Article
- Anti-cancer activity of a novel small molecule compound that simultaneously activates p53 and inhibits NF-κB signaling.PloS one · 2012Article
- The Role of Pharmacokinetics and Pharmacodynamics in Early Drug Development with reference to the Cyclin-dependent Kinase (Cdk) Inhibitor - Roscovitine.Sultan Qaboos University medical journal · 2011Article
- Serine 312 phosphorylation is dispensable for wild-type p53 functions in vivo.Cell death and differentiation · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 tumor suppressor is regulated by the MDM2 oncoprotein. Overexpression of MDM2 maintains p53 at low levels and contributes to the functional inactivation of p53 in a subset of tumors. We found that treatment with roscovitine and olomoucin, which were originally developed as cyclin-dependent kinase (CDK) inhibitors, can efficiently stabilize and activate nuclear p53 in tumor cells with MDM2 amplification or cytoplasmic p53. These inhibitors block the degradation of p53 without affecting p53-MDM2 binding and the nuclear shuttling function of p53 and MDM2. Roscovitine also induces stabilization of the p53 Ala-315 mutant, indicating that it does not act by regulating the CDK phosphorylation of serine 315. Roscovitine induces down-regulation of MDM2 expression at both protein and mRNA levels. Ectopic expression of MDM2 can abrogate the ability of roscovitine to induce p53 stabilization. Low concentrations of roscovitine cooperate with the DNA-damaging agent camptothecin to activate p53 in a synergistic fashion. These results show that the small molecule CDK inhibitors can be used to activate p53 through their potent inhibitory effect on MDM2 expression and may be useful as sensitizing agents for other DNA-damaging drugs.
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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.