ArticleMolecular and cellular biology2012
MdmX is required for p53 interaction with and full induction of the Mdm2 promoter after cellular stress.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Loci influencing blood pressure identified using a cardiovascular gene-centric array.Human molecular genetics · 2013Pooled it
- Targeting Hdm2 and Hdm4 in Anticancer Drug Discovery: Implications for Checkpoint Inhibitor Immunotherapy.Cells · 2024Review
- MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.Cell death & disease · 2020Article
- Evaluation of TP53 Pro72Arg and MDM2 SNP285-SNP309 polymorphisms in an Italian cohort of LFS suggestive patients lacking identifiable TP53 germline mutations.Familial cancer · 2016Article
- Estrogen receptor alpha (ERα/ESR1) mediates the p53-independent overexpression of MDM4/MDMX and MDM2 in human breast cancer.Oncotarget · 2016Article
- Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.Cell death & disease · 2015Article
- Article
- Doxorubicin and 5-fluorouracil induced accumulation and transcriptional activity of p53 are independent of the phosphorylation at serine 15 in MCF-7 breast cancer cells.Cancer biology & therapy · 2014Article
- Deubiquitinating enzyme regulation of the p53 pathway: A lesson from Otub1.World journal of biological chemistry · 2014Review
- The regulation of MDM2 oncogene and its impact on human cancers.Acta biochimica et biophysica Sinica · 2014Review
- Targeting p53-MDM2-MDMX loop for cancer therapy.Sub-cellular biochemistry · 2014Review
- Cisplatin causes cell death via TAB1 regulation of p53/MDM2/MDMX circuitry.Genes & development · 2013Article
- Article
- p53 Regulation Goes Live-Mdm2 and MdmX Co-Star: Lessons Learned from Mouse Modeling.Genes & cancer · 2012Article
- Protecting the genome from mdm2 and mdmx.Genes & cancer · 2012Article
- Mdm2 and MdmX as Regulators of Gene Expression.Genes & cancer · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The activity of the tumor suppressor p53 is tightly controlled by its main negative regulator, Mdm2, which inhibits p53's transcriptional activity and targets it for degradation via the proteasome pathway. The closely related Mdm2 homolog, MdmX, is also considered to be a general inhibitor of transactivation by p53, through binding to the p53 activation domain. We show here that, unexpectedly, upon DNA damage and ribosomal stress, MdmX plays a positive role in p53-mediated activation of the Mdm2 gene, but not of numerous other p53 target genes including p21. Downregulation of MdmX results in lower levels of mature and nascent Mdm2 transcripts following cellular stress. This correlates with a longer p53 half-life following DNA damage. In vitro, Mdm2 inhibits the binding of p53 to DNA to a much greater extent than does MdmX, although MdmX does not stimulate p53 interaction with Mdm2 promoter DNA. Strikingly, however, MdmX is required for optimal p53 binding to the Mdm2 promoter in vivo. Thus, we have described a new mechanism by which MdmX can suppress p53, which is through transcriptional activation of p53's principal negative regulator, Mdm2.
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.