ArticleMolecular and cellular biology2007
Mdm2 is required for inhibition of Cdk2 activity by p21, thereby contributing to p53-dependent cell cycle arrest.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
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- Biodegradable Nanoparticles Encapsulating Murine Double Minute 2 siRNA to Treat Peritoneal Dissemination of Colon Cancer.International journal of molecular sciences · 2025Article
- Functional evaluation of germline TP53 variants identified in Brazilian families at-risk for Li-Fraumeni syndrome.Scientific reports · 2024Article
- CENPN contributes to pancreatic carcinoma progression through the MDM2-mediated p53 signaling pathway.Archives of medical science : AMS · 2024Article
- Review
- KDM4 inhibitor SD49-7 attenuates leukemia stem cellTheranostics · 2022Article
- The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity.The Journal of experimental medicine · 2021Article
- Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence.The Journal of cell biology · 2019Article
- Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer.Frontiers in oncology · 2019Article
- Long non-coding RNA Lnc-Tim3 exacerbates CD8 T cell exhaustion via binding to Tim-3 and inducing nuclear translocation of Bat3 in HCC.Cell death & disease · 2018Article
- CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss.The Journal of experimental medicine · 2018Article
- Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase.Oncogene · 2017Article
- Dependence of p53-deficient cells on the DHX9 DExH-box helicase.Oncotarget · 2017Article
- Characterization of Lgr5+ Progenitor Cell Transcriptomes after Neomycin Injury in the Neonatal Mouse Cochlea.Frontiers in molecular neuroscience · 2017Article
- Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism.Journal of food and drug analysis · 2016Article
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- Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.Cell death & disease · 2015Article
- Induction of Mitochondrial Dependent Apoptosis in Human Leukemia K562 Cells by Meconopsis integrifolia: A Species from Traditional Tibetan Medicine.Molecules (Basel, Switzerland) · 2015Article
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
p53 is extensively posttranslationally modified in response to various types of cellular stress. Such modifications have been implicated in the regulation of p53 protein levels as well as its DNA binding and transcriptional activities. Treatment of cells with doxorubicin causes phosphorylation and acetylation of p53, transcriptional upregulation of p21 and other target genes, and growth arrest. In contrast, downregulation of Mdm2 by a small interfering RNA (siRNA) approach led to increased levels of p53 lacking phosphorylation at serine 15 and acetylation at lysine 382. Levels of binding of p53 to the p21 promoter were comparable following treatment with doxorubicin or Mdm2 siRNA. Moreover, p53 was transcriptionally active and capable of inducing or repressing a variety of its target genes. Surprisingly, p53 upregulated by Mdm2 siRNA had no effect on cell cycle progression. Although comparable in level to that achieved by treatment with the p53 activators actinomycin D and nutlin-3, the increases in p53 and p21 after downregulation of Mdm2 were not sufficient to trigger cell cycle arrest. This version of p21 was capable of interacting with cyclin-dependent kinase 2 (Cdk2) but failed to inhibit its activity. Taken together, these results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest.
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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.