ArticleProceedings of the National Academy of Sciences of the United States of America2009
Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 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
123 citing papers in PubMed, 217 citations in OpenAlex.
- Targeting p300/CBP destabilizes HIF-2α and suppresses tumor growth in cell and animal models of clear cell renal cell carcinoma.Cancer letters · 2026Article
- Article
- Dynamic control of IDP interaction network via diverse binding pathways.Nature communications · 2026Article
- The Allosteric Regulation of the DNA-Binding Domain of p53 by the Intrinsically Disordered C-Terminal Domain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- CBP/p300, a promising therapeutic target for prostate cancer.Journal of translational medicine · 2025Review
- Multiple transactivation domains of EZH2 bind to the TAZ2 domain of p300 and stimulate the acetyltransferase function of p300.The Biochemical journal · 2025Article
- Versatile roles of disordered transcription factor effector domains in transcriptional regulation.The FEBS journal · 2025Review
- How does p53 work? Regulation by the intrinsically disordered domains.Trends in biochemical sciences · 2025Review
- Identification of a novel, pathogenicFrontiers in genetics · 2025Article
- Molecular basis of the interactions between the disordered Neh4 and Neh5 domains of Nrf2 and CBP/p300 in oxidative stress response.Protein science : a publication of the Protein Society · 2024Article
- Structural Adaptation of Secondary p53 Binding Sites on MDM2 and MDMX.Journal of molecular biology · 2024Article
- Article
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
- Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes.Molecular biology and evolution · 2024Article
- DescribePROT in 2023: more, higher-quality and experimental annotations and improved data download options.Nucleic acids research · 2024Article
- The C-terminal transactivation domain of MITF interacts promiscuously with co-activator CBP/p300.Scientific reports · 2023Article
- TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition.Nature communications · 2023Article
- Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review.International journal of molecular sciences · 2023Review
- 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
- Pharmacological targeting of CBP/p300 drives a redox/autophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells.Cancer gene therapy · 2023Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The tumor suppressor activity of p53 is regulated by interactions with the ubiquitin ligase HDM2 and the general transcriptional coactivators CBP and p300. Using NMR spectroscopy and isothermal titration calorimetry, we have dissected the binding interactions between the N-terminal transactivation domain (TAD) of p53, the TAZ1, TAZ2, KIX, and nuclear receptor coactivator binding domains of CBP, and the p53-binding domain of HDM2. The p53 TAD contains amphipathic binding motifs within the AD1 and AD2 regions that mediate interactions with CBP and HDM2. Binding of the p53 TAD to CBP domains is dominated by interactions with AD2, although the affinity is enhanced by additional interactions with AD1. In contrast, binding of p53 TAD to HDM2 is mediated primarily by AD1. The p53 TAD can bind simultaneously to HDM2 (through AD1) and to any one of the CBP domains (through AD2) to form a ternary complex. Phosphorylation of p53 at T18 impairs binding to HDM2 and enhances affinity for the CBP KIX domain. Multisite phosphorylation of the p53 TAD at S15, T18, and S20 leads to increased affinity for the TAZ1 and KIX domains of CBP. These observations suggest a mechanism whereby HDM2 and CBP/p300 function synergistically to regulate the p53 response. In unstressed cells, CBP/p300, HDM2 and p53 form a ternary complex that promotes polyubiquitination and degradation of p53. After cellular stress and DNA damage, p53 becomes phosphorylated at T18 and other residues in the AD1 region, releases HDM2 and binds preferentially to CBP/p300, leading to stabilization and activation of p53.
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.