ArticleProtein science : a publication of the Protein Society2018
p53 promotes its own polyubiquitination by enhancing the HDM2 and HDMX interaction.
Article in Protein science : a publication of the Protein Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Reduced structural rigidity of MDMX protein enhances binding to TP53 mRNA.Bioscience reports · 2025Article
- Ferroptosis-Related Transcriptional Level Changes and the Role of CIRBP in Glioblastoma Cells Ferroptosis.Biomedicines · 2024Article
- Choosing the Right Cell Line for Acute Myeloid Leukemia (AML) Research.International journal of molecular sciences · 2023Review
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- 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
- Loss of BRMS2 induces cell growth inhibition and translation capacity reduction in colorectal cancer cells.American journal of cancer research · 2021Article
- Molecular and Biochemical Techniques for Deciphering p53-MDM2 Regulatory Mechanisms.Biomolecules · 2020Review
- MDM2's dual mRNA binding domains co-ordinate its oncogenic and tumour suppressor activities.Nucleic acids research · 2020Article
- Analysis of the p53 pathway in peripheral blood of retinoblastoma patients; potential biomarkers.PloS one · 2020Article
- The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276.Cellular & molecular biology letters · 2020Article
- Review
- Allosteric changes in HDM2 by the ATM phosphomimetic S395D mutation: implications on HDM2 function.The Biochemical journal · 2019Article
- The p53 mRNA: an integral part of the cellular stress response.Nucleic acids research · 2019Review
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HDM2 and HDMX are two homologs essential for controlling p53 tumor suppressor activity under normal conditions. Both proteins bind different sites on the p53 N-terminus, and while HDM2 has E3 ubiquitin ligase activity towards p53, HDMX does not. Nevertheless, HDMX is required for p53 polyubiquitination and degradation, but the underlying molecular mechanism remains unclear. Alone, HDMX and HDM2 interact via their respective C-terminal RING domains but here we show that the presence of p53 induces an N-terminal interface under normal cellular conditions. This results in an increase in HDM2-mediated p53 polyubiquitination and degradation. The HDM2 inhibitor Nutlin-3 binds the N-terminal p53 binding pocket and is sufficient to induce the HDM2-HDMX interaction, suggesting that the mechanism depends on allosteric changes that control the multiprotein complex formation. These results demonstrate an allosteric interchange between three different proteins (HDMX-HDM2-p53) and help to explain the molecular mechanisms of HDM2-inhibitory drugs.
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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.