ArticleProceedings of the National Academy of Sciences of the United States of America2015
Autoinhibition of MDMX by intramolecular p53 mimicry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting the MDM2-MDM4 interaction interface reveals an otherwise therapeutically active wild-type p53 in colorectal cancer.Molecular oncology · 2025Article
- MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Cellular carcinogenesis in preleukemic conditions:drivers and defenses.Fukushima journal of medical science · 2024Review
- MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.Biologics : targets & therapy · 2024Review
- The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX.Journal of molecular biology · 2022Article
- Review
- Helical sulfono-γ-AApeptides with predictable functions in protein recognition.RSC chemical biology · 2022Review
- MDMX Recruits UbcH5c to Facilitate MDM2 E3 Ligase Activity and Subsequent p53 DegradationCancer research · 2021Article
- MDM4 alternative splicing and implication in MDM4 targeted cancer therapies.American journal of cancer research · 2021Review
- Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions.Journal of medicinal chemistry · 2020Article
- MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.The EMBO journal · 2020Article
- Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.Frontiers in oncology · 2020Review
- Disorder for Dummies: Functional Mutagenesis of Transient Helical Segments in Disordered Proteins.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Mutual regulation of MDM4 and TOP2A in cancer cell proliferation.Molecular oncology · 2019Article
- 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
- Kinetic and thermodynamic effects of phosphorylation on p53 binding to MDM2.Scientific reports · 2019Article
- Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.Proceedings of the National Academy of Sciences of the United States of America · 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
- MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The p53 inhibitor MDMX is controlled by multiple stress signaling pathways. Using a proteolytic fragment release (PFR) assay, we detected an intramolecular interaction in MDMX that mechanistically mimics the interaction with p53, resulting in autoinhibition of MDMX. This mimicry is mediated by a hydrophobic peptide located in a long disordered central segment of MDMX that has sequence similarity to the p53 transactivation domain. NMR spectroscopy was used to show this hydrophobic peptide interacts with the N-terminal domain of MDMX in a structurally analogous manner to p53. Mutation of two critical tryptophan residues in the hydrophobic peptide disrupted the intramolecular interaction and increased p53 binding, providing further evidence for mechanistic mimicry. The PFR assay also revealed a second intramolecular interaction between the RING domain and central region that regulates MDMX nuclear import. These results establish the importance of intramolecular interactions in MDMX regulation, and validate a new assay for the study of intramolecular interactions in multidomain proteins with intrinsically disordered regions.
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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.