ArticleMolecular and cellular biology2016
Allosteric Interactions by p53 mRNA Govern HDM2 E3 Ubiquitin Ligase Specificity under Different Conditions.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 24 citations in OpenAlex.
- Reduced structural rigidity of MDMX protein enhances binding to TP53 mRNA.Bioscience reports · 2025Article
- TheiScience · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Cryptic in vitro ubiquitin ligase activity of HDMX towards p53 is probably regulated by an induced fit mechanism.Bioscience reports · 2022Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Review
- miR-10a as a therapeutic target and predictive biomarker for MDM2 inhibition in acute myeloid leukemia.Leukemia · 2021Article
- MDM2 regulates RB levels during genotoxic stress.EMBO reports · 2021Article
- Molecular and Biochemical Techniques for Deciphering p53-MDM2 Regulatory Mechanisms.Biomolecules · 2020Review
- Analysis of the p53 pathway in peripheral blood of retinoblastoma patients; potential biomarkers.PloS one · 2020Article
- Entire ABL1 Gene Deletion Without BCR/ABL1 Rearrangement in a Female Patient with B-Cell Precursor Acute Lymphoblastic Leukemia.OncoTargets and therapy · 2020Article
- Allosteric changes in HDM2 by the ATM phosphomimetic S395D mutation: implications on HDM2 function.The Biochemical journal · 2019Article
- Shaping the regulation of the p53 mRNA tumour suppressor: the co-evolution of genetic signatures.BMC cancer · 2019Review
- The p53 mRNA: an integral part of the cellular stress response.Nucleic acids research · 2019Review
- A single synonymous mutation determines the phosphorylation and stability of the nascent protein.Journal of molecular cell biology · 2019Article
- p53 promotes its own polyubiquitination by enhancing the HDM2 and HDMX interaction.Protein science : a publication of the Protein Society · 2018Article
- Ubiquitin-dependent proteolysis of CXCL7 leads to posterior longitudinal ligament ossification.PloS one · 2018Article
- Fanconi Anemia Signaling and Cancer.Trends in cancer · 2017Review
- MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer.Journal of hematology & oncology · 2017Review
- Dual function of MDM2 and MDMX toward the tumor suppressors p53 and RB.Genes & cancer · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HDM2 and HDMX are key negative regulatory factors of the p53 tumor suppressor under normal conditions by promoting its degradation or preventing its trans activity, respectively. It has more recently been shown that both proteins can also act as positive regulators of p53 after DNA damage. This involves phosphorylation by ATM on serine residues HDM2(S395) and HDMX(S403), promoting their respective interaction with the p53 mRNA. However, the underlying molecular mechanisms of how these phosphorylation events switch HDM2 and HDMX from negative to positive regulators of p53 is not known. Our results show that these phosphorylation events reside within intrinsically disordered domains and change the conformation of the proteins. The modifications promote the exposition of N-terminal interfaces that support the formation of a new HDMX-HDM2 heterodimer independent of the C-terminal RING-RING interaction. The E3 ubiquitin ligase activity of this complex toward p53 is prevented by the p53 mRNA ligand but, interestingly, does not affect the capacity to ubiquitinate HDMX and HDM2. These results show how ATM-mediated modifications of HDMX and HDM2 switch HDM2 E3 ubiquitin ligase activity away from p53 but toward HDMX and itself and illustrate how the substrate specificity of HDM2 E3 ligase activity is regulated.
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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.