ArticleMolecular and cellular biology2014
Autoactivation of the MDM2 E3 ligase by intramolecular interaction.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Dual functionality of MDM2 in PROTACs expands the horizons of targeted protein degradation.Biomarker research · 2025Review
- Ribosomal Protein S4 X-Linked as a Novel Modulator of MDM2 Stability by Suppressing MDM2 Auto-Ubiquitination and SCF Complex-Mediated Ubiquitination.Biomolecules · 2024Article
- Bivalent binding of p14ARF to MDM2 RING and acidic domains inhibits E3 ligase function.Life science alliance · 2022Article
- MDMX Recruits UbcH5c to Facilitate MDM2 E3 Ligase Activity and Subsequent p53 DegradationCancer research · 2021Article
- Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity.Molecular and cellular biology · 2019Article
- A Single Conserved Amino Acid Residue as a Critical Context-Specific Determinant of the Differential Ability of Mdm2 and MdmX RING Domains to Dimerize.Frontiers in physiology · 2019Article
- Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity.Nature structural & molecular biology · 2017Article
- Acetylation-dependent regulation of MDM2 E3 ligase activity dictates its oncogenic function.Science signaling · 2017Article
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Intra molecular interactions in the regulation of p53 pathway.Translational cancer research · 2016Article
- Allosteric Interactions by p53 mRNA Govern HDM2 E3 Ubiquitin Ligase Specificity under Different Conditions.Molecular and cellular biology · 2016Article
- Ribosomal protein L4 is a novel regulator of the MDM2-p53 loop.Oncotarget · 2016Article
- Characterization of cancer-associated missense mutations in MDM2.Molecular & cellular oncology · 2016Article
- Article
- Hyperglycemia promotes p53-Mdm2 interaction but reduces p53 ubiquitination in RINm5F cells.Molecular and cellular biochemistry · 2015Article
- Autoinhibition of MDMX by intramolecular p53 mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The RING domain ubiquitin E3 ligase MDM2 is a key regulator of p53 degradation and a mediator of signals that stabilize p53. The current understanding of the mechanisms by which MDM2 posttranslational modifications and protein binding cause p53 stabilization remains incomplete. Here we present evidence that the MDM2 central acidic region is critical for activating RING domain E3 ligase activity. A 30-amino-acid minimal region of the acidic domain binds to the RING domain through intramolecular interactions and stimulates the catalytic function of the RING domain in promoting ubiquitin release from charged E2. The minimal activation sequence is also the binding site for the ARF tumor suppressor, which inhibits ubiquitination of p53. The acidic domain-RING domain intramolecular interaction is modulated by ATM-mediated phosphorylation near the RING domain or by binding of ARF. These results suggest that MDM2 phosphorylation and association with protein regulators share a mechanism in inhibiting the E3 ligase function and stabilizing p53 and suggest that targeting the MDM2 autoactivation mechanism may be useful for therapeutic modulation of p53 levels.
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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.