ArticleBiochemistry2016
Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain Ligand I-CBP112.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Transcriptome and acetylome profiling identify crucial steps of neuronal differentiation in Rubinstein-Taybi syndrome.Communications biology · 2024Article
- Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.Nature communications · 2024Article
- Chromosome-Wide Distribution and Characterization of H3K36me3 and H3K27Ac in the Marine Model DiatomPlants (Basel, Switzerland) · 2023Article
- High-Throughput Identification of Epigenetic Compounds to Enhance Chicken Host Defense Peptide Gene Expression.Antibiotics (Basel, Switzerland) · 2022Article
- EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma.Cancer discovery · 2022Article
- p300 suppresses the transition of myelodysplastic syndromes to acute myeloid leukemia.JCI insight · 2021Article
- Article
- Controlling Intramolecular Interactions in the Design of Selective, High-Affinity Ligands for the CREBBP Bromodomain.Journal of medicinal chemistry · 2021Article
- Review
- The Chemical Biology of Reversible Lysine Post-translational Modifications.Cell chemical biology · 2020Review
- Selective Modulation of Dynamic Protein Complexes.Cell chemical biology · 2020Review
- Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734.Molecular cancer therapeutics · 2020Article
- Chemoenzymatic Semisynthesis of Proteins.Chemical reviews · 2020Review
- Chromatin accessibility promotes hematopoietic and leukemia stem cell activity.Nature communications · 2020Article
- Impact of HDAC Inhibitors on Protein Quality Control Systems: Consequences for Precision Medicine in Malignant Disease.Frontiers in cell and developmental biology · 2020Review
- Review
- MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma.Cancer research · 2019Article
- Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP.Biochemistry · 2019Article
- Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation.Molecules (Basel, Switzerland) · 2018Review
- Modulating the masters: chemical tools to dissect CBP and p300 function.Current opinion in chemical biology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The histone acetyltransferase (HAT) enzymes p300 and CBP are closely related paralogs that serve as transcriptional coactivators and have been found to be dysregulated in cancer and other diseases. p300/CBP is a multidomain protein and possesses a highly conserved bromodomain that has been shown to bind acetylated Lys residues in both proteins and various small molecules, including I-CBP112 and CBP30. Here we show that the ligand I-CBP112 can stimulate nucleosome acetylation up to 3-fold while CBP30 does not. Activation of p300/CBP by I-CBP112 is not observed with the isolated histone H3 substrate but requires a nucleosome substrate. I-CBP112 does not impact nucleosome acetylation by the isolated p300 HAT domain, and the effects of I-CBP112 on p300/CBP can be neutralized by CBP30, suggesting that I-CBP112 likely allosterically activates p300/CBP through bromodomain interactions. Using mass spectrometry and Western blots, we have found that I-CBP112 particularly stimulates acetylation of Lys18 of histone H3 (H3K18) in nucleosomes, an established in vivo site of p300/CBP. In addition, we show that I-CBP112 enhances H3K18 acetylation in acute leukemia and prostate cancer cells in a concentration range commensurate with its antiproliferative effects. Our findings extend the known pharmacology of bromodomain ligands in the regulation of p300/CBP and suggest a novel approach to modulating histone acetylation in cancer.
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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.