ArticleProceedings of the National Academy of Sciences of the United States of America2010
Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- The association of GNAS defects with pro-inflammatory adipokine levels in pseudohypoparathyroidism type 1.Journal of endocrinological investigation · 2026Article
- Dynamic control of IDP interaction network via diverse binding pathways.Nature communications · 2026Article
- Phosphorylation-dependent tuning of mRNA deadenylation rates.Nature structural & molecular biology · 2026Article
- Linker Length and Composition within Disordered Binding Motifs Modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch.Journal of molecular biology · 2025Article
- Rubinstein-Taybi Syndrome: A Comprehensive Analysis of a Polish Cohort with Most Cases Due to NovelGenes · 2025Article
- Opto-p53: A light-controllable activation of p53 signaling pathway.Cell structure and function · 2025Article
- FINCHES: A Computational Framework for Predicting Intermolecular Interactions in Intrinsically Disordered Proteins.International journal of molecular sciences · 2025Review
- Differences in the role of Gper1 in colorectal cancer progression depending on sex.Oncology letters · 2025Article
- Article
- How does p53 work? Regulation by the intrinsically disordered domains.Trends in biochemical sciences · 2025Review
- Dynamic O-GlcNAcylation coordinates etoposide-triggered tumor cell pyroptosis by regulating p53 stability.The Journal of biological chemistry · 2025Article
- Multivalent Protein-Nucleic Acid Interactions Probed by Composition-Gradient Multiangle Light Scattering.ACS omega · 2024Article
- A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions.Angewandte Chemie (International ed. in English) · 2024Article
- 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
- Using High-Throughput Measurements to Identify Principles of Transcriptional and Epigenetic Regulators.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Interaction modules that impart specificity to disordered protein.Trends in biochemical sciences · 2023Review
- Control of protein stability by post-translational modifications.Nature communications · 2023Review
- How phosphorylation impacts intrinsically disordered proteins and their function.Essays in biochemistry · 2022Article
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
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The transcriptional activity of p53 is regulated by a cascade of posttranslational modifications. Although acetylation of p53 by CREB-binding protein (CBP)/p300 is known to be indispensable for p53 activation, the role of phosphorylation, and in particular multisite phosphorylation, in activation of CBP/p300-dependent p53 transcriptional pathways remains unclear. We investigated the role of single site and multiple site phosphorylation of the p53 transactivation domain in mediating its interaction with CBP and with the ubiquitin ligase HDM2. Phosphorylation at Thr18 functions as an on/off switch to regulate binding to the N-terminal domain of HDM2. In contrast, binding to CBP is modulated by the extent of p53 phosphorylation; addition of successive phosphoryl groups enhances the affinity for the TAZ1, TAZ2, and KIX domains of CBP in an additive manner. Activation of p53-dependent transcriptional pathways requires that p53 compete with numerous cellular transcription factors for binding to limiting amounts of CBP/p300. Multisite phosphorylation represents a mechanism for a graded p53 response, with each successive phosphorylation event resulting in increasingly efficient recruitment of CBP/p300 to p53-regulated transcriptional programs, in the face of competition from cellular transcription factors. Multisite phosphorylation thus acts as a rheostat to enhance binding to CBP/p300 and provides a plausible mechanistic explanation for the gradually increasing p53 response observed following prolonged or severe genotoxic stress.
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.