ArticleCell cycle (Georgetown, Tex.)2015
Structural convergence of unstructured p53 family transactivation domains in MDM2 recognition.
Article in Cell cycle (Georgetown, Tex.), 2015. 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
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, 28 citations in OpenAlex.
- Integrative Modeling of Protein-Polypeptide Complexes by Bayesian Model Selection using AlphaFold and NMR Chemical Shift Perturbation Data.bioRxiv : the preprint server for biology · 2024Article
- New insights into cancer: MDM2 binds to the citrullinating enzyme PADI4.Protein science : a publication of the Protein Society · 2023Article
- Evolution of affinity between p53 transactivation domain and MDM2 across the animal kingdom demonstrates high plasticity of motif-mediated interactions.Protein science : a publication of the Protein Society · 2023Article
- Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.International journal of molecular sciences · 2022Article
- Structural diversity of p63 and p73 isoforms.Cell death and differentiation · 2022Review
- Single-molecule analysis of interaction between p53TAD and MDM2 using aerolysin nanopores.Chemical science · 2021Article
- Towards reconstructing the dipteran demise of an ancient essential gene: E3 ubiquitin ligase Murine double minute.Development genes and evolution · 2020Article
- AlphaSpace 2.0: Representing Concave Biomolecular Surfaces Using β-Clusters.Journal of chemical information and modeling · 2020Article
- Simulation of MDM2 N-terminal domain conformational lability in the presence of imidazoline based inhibitors of MDM2-p53 protein-protein interaction.Journal of computer-aided molecular design · 2020Article
- Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway.International journal of molecular sciences · 2019Review
- Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-XThe Journal of biological chemistry · 2018Article
- Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25.Molecules (Basel, Switzerland) · 2018Article
- Article
- Evolution of the p53-MDM2 pathway.BMC evolutionary biology · 2017Article
- The Regulation of Tumor Suppressor p63 by the Ubiquitin-Proteasome System.International journal of molecular sciences · 2016Review
- Structure and apoptotic function of p73.BMB reports · 2015Review
- Accelerating physical simulations of proteins by leveraging external knowledge.Wiley interdisciplinary reviews. Computational molecular scienceArticle
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 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53, p63, and p73 proteins belong to the p53 family of transcription factors, which play key roles in tumor suppression. Although the transactivation domains (TADs) of the p53 family are intrinsically disordered, these domains are commonly involved in the regulatory interactions with mouse double minute 2 (MDM2). In this study, we determined the solution structure of the p73TAD peptide in complex with MDM2 using NMR spectroscopy and biophysically characterized the interactions between the p53 family TAD peptides and MDM2. In combination with mutagenesis data, the complex structures revealed remarkably close mimicry of the MDM2 recognition mechanism among the p53 family TADs. Upon binding with MDM2, the intrinsically disordered p73TAD and p63TAD peptides adopt an amphipathic α-helical conformation, which is similar to the conformation of p53TAD, although the α-helical content induced by MDM2 binding varies. With isothermal titration calorimetry (ITC) and circular dichroism (CD) data, our biophysical characterization showed that p73TAD resembles p53TAD more closely than p63TAD in terms of helical stability, MDM2 binding affinity, and phosphorylation effects on MDM2 binding. Therefore, our structural information may be useful in establishing alternative anticancer strategies that exploit the activation of the p73 pathway against human tumors bearing p53 mutations.
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.