| 1993 |
p300 co-precipitates with TATA-binding protein (TBP) in a specific, SDS-sensitive complex, and p300-specific and TBP-specific complexes share at least two common phosphoproteins (64 kDa and 59 kDa), indicating p300 interacts with TBP and is a component of the basal transcriptional machinery. |
Co-immunoprecipitation, partial proteolytic digest pattern matching |
Oncogene |
Medium |
8502484
|
| 1997 |
p300 binds directly to the tumor suppressor p53 in the absence of viral oncoproteins; they colocalize in the nucleus and coexist in a stable DNA-binding complex. p300 acts as a transcriptional adaptor for p53, modulating its G1 checkpoint and apoptosis functions. E1A disrupts p300/p53-dependent growth control. |
Co-immunoprecipitation, co-localization, functional promoter assays (p21, bax), cell-cycle and apoptosis assays |
Nature |
High |
9194565
|
| 2000 |
p300 and CBP acetylate MyoD on two lysines at the boundary of the DNA-binding domain in vitro; this acetylation activates MyoD transcriptional activity on a muscle-specific promoter. MyoD mutants that cannot be acetylated are not functionally activated. |
In vitro acetylation assay, microinjection functional assay, mutagenesis |
The Journal of biological chemistry |
High |
10944526
|
| 2000 |
Protein kinase C phosphorylates p300 at serine 89 in vivo; this phosphorylation represses the transcriptional activity of p300, representing a signal transduction pathway for PKC to regulate cell growth and differentiation. |
In vivo phosphorylation mapping, kinase assay, transcriptional reporter assay |
The Journal of biological chemistry |
Medium |
11020388
|
| 2000 |
EID-1 binds p300 and inhibits its histone acetyltransferase activity, thereby repressing MyoD-dependent transcription in skeletal muscle independently of its Rb-binding function. |
Yeast two-hybrid, co-immunoprecipitation, HAT activity assay, transcriptional reporter assay |
Molecular and cellular biology |
Medium |
11073990
|
| 2003 |
p29ING4 and p28ING5 physically interact with p300 in vivo and enhance p300-mediated acetylation of p53 at Lys-382, thereby activating p53-dependent transcription and apoptosis. |
Co-immunoprecipitation, in vivo acetylation assay, transcriptional reporter assay (p21/waf1 promoter) |
Cancer research |
Medium |
12750254
|
| 2003 |
p68 RNA helicase directly interacts with multiple domains of CBP/p300 and with RNA Pol II in vivo and in vitro; p68 stimulates CBP/p300-mediated transcription in a cooperative manner, and E1A suppression of CBP/p300 abolishes p68-driven transcription. |
Co-immunoprecipitation, GST pulldown, transcriptional reporter assay |
Oncogene |
Medium |
12527917
|
| 2005 |
p300 potentiates Sox9-dependent transcription specifically on chromatinized (nucleosomal) DNA templates but not on naked DNA, and this is associated with p300-mediated histone hyperacetylation around the collagen α1(II) enhancer. |
In vitro transcription on chromatinized templates, recombinant protein association assay, ChIP |
The Journal of biological chemistry |
High |
16109717
|
| 2006 |
Nuclear ROCK2 associates with and phosphorylates p300 both in vitro and in cells; ROCK2-mediated phosphorylation of p300 increases its acetyltransferase activity in vitro. |
Co-immunoprecipitation, in vitro kinase assay, gel filtration, immunofluorescence co-localization, HAT activity assay |
The Journal of biological chemistry |
Medium |
16574662
|
| 2009 |
p300 and CBP function as cytoplasmic E4 polyubiquitin ligases for p53. The E3/E4 ubiquitin ligase activity resides exclusively in cytoplasmic fractions; the N-terminal ~595 aa of p300 encode both E3 and p53-directed E4 activities. CBP deficiency specifically stabilizes cytoplasmic, but not nuclear, p53. |
Subcellular fractionation, in vitro ubiquitination assay, co-immunoprecipitation, loss-of-function cell lines (p300/CBP-deficient) |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19805293
|
| 2009 |
KAT3B/p300 acetylates transition protein 2 (TP2) more efficiently than PCAF in vitro, targeting four lysine residues in the C-terminal domain. Acetylation of TP2 by p300 reduces its DNA condensation ability and impedes its interaction with the histone chaperone NPM3. |
In vitro acetyltransferase assay, mass spectrometry, circular dichroism, atomic force microscopy, in vivo acetylation |
The Journal of biological chemistry |
High |
19710011
|
| 2009 |
The natural hydroxynaphthoquinone plumbagin inhibits p300 HAT activity in a non-competitive manner in vitro and in vivo, specifically blocking p300-mediated (but not PCAF-mediated) acetylation of p53. Site-directed mutagenesis of K1358 in the HAT domain abolishes inhibitor binding. |
In vitro HAT assay, in vivo p53 acetylation assay, molecular docking, site-directed mutagenesis |
The Journal of biological chemistry |
High |
19570987
|
| 2014 |
BAG6 regulates nuclear localization of EP300; in the absence of BAG6, EP300 accumulates in the cytoplasm. BAG6 interaction with EP300 occurs in the cytoplasm and during starvation promotes EP300 translocation to the nucleus, where it acetylates p53 (pro-autophagic) while reducing cytoplasmic acetylation of ATG5, ATG7, and LC3-I (which inhibit autophagy). |
Subcellular fractionation, co-immunoprecipitation, loss-of-function (knockout MEFs), acetylation assays, autophagy assays |
Autophagy |
Medium |
24852146
|
| 2015 |
p300 has both acetyltransferase and crotonyltransferase activities; p300-catalyzed histone crotonylation directly stimulates transcription to a greater degree than histone acetylation. Cellular crotonyl-CoA concentration regulates histone crotonylation levels and thereby gene expression. |
In vitro enzymatic assay, cell-based transcription assay, genetic/environmental perturbation of crotonyl-CoA levels, ChIP |
Molecular cell |
High |
25818647
|
| 2015 |
DDX24 interacts with p300 and suppresses p300-mediated acetylation of p53. DDX24 overexpression inhibits the p300-p53 interaction; knockdown of DDX24 increases p53 acetylation levels, activates p53 target genes (p21, PUMA), and induces cell cycle arrest and senescence in a p53-dependent manner. |
Co-immunoprecipitation, RNA interference, in vivo acetylation assay, transcriptional target expression |
Oncogene |
Medium |
25867071
|
| 2017 |
mTORC1 directly interacts with p300 and phosphorylates it at four serine residues in the C-terminal domain. This phosphorylation prevents the HAT domain from binding the RING domain, relieving intramolecular autoinhibition of p300. mTORC1-dependent p300 phosphorylation suppresses starvation-induced autophagy and activates lipogenesis. |
Co-immunoprecipitation, in vitro kinase assay, domain interaction mapping, functional autophagy and lipogenesis assays |
Molecular cell |
High |
29033323
|
| 2018 |
p300 functions as a lysine 2-hydroxyisobutyryltransferase (Khib writer), targeting distinct sites from its acetylation targets. p300-catalyzed Khib on glycolytic enzymes (e.g., ENO1) regulates their catalytic activity; p300 deletion reduces Khib on these enzymes, impairs glycolysis, and sensitizes cells to glucose deprivation-induced death. |
In vitro enzymatic assay, quantitative proteomics (SILAC), mass spectrometry, genetic deletion (p300 KO cells), metabolic activity assay |
Molecular cell |
High |
29775581
|
| 2018 |
Transcription factor dimerization (IRF3, STAT1) activates p300 by enabling trans-autoacetylation of p300's autoinhibitory lysine-rich loop. A crystal structure of p300 shows the autoinhibitory loop invading the active site of a neighboring HAT domain, capturing a trans-autoacetylation intermediate. The RING domain also has an autoinhibitory role requiring rearrangement for substrate access. |
Crystal structure, in vitro HAT assay, mutagenesis, transcription factor dimerization assays |
Nature |
High |
30323286
|
| 2018 |
DYRK1A physically interacts with p300 and CBP; overexpression of DYRK1A causes hyperphosphorylation of p300/CBP. ChIP-seq shows DYRK1A co-localizes with p300/CBP at enhancers; DYRK1A knockdown reduces H3K27ac at these enhancers, indicating DYRK1A modulates p300/CBP acetyltransferase activity at enhancers. |
Proteomics (mass spectrometry), co-immunoprecipitation, ChIP-seq, shRNA knockdown with H3K27ac readout |
Nucleic acids research |
Medium |
30137413
|
| 2019 |
EP300 controls enhancer acetylation by interacting with TFAP2β, a lineage-defining transcription factor in MYCN-amplified neuroblastoma. EP300 (but not CBP) is essential for H3K27ac at core regulatory circuitry enhancers; PROTAC-mediated degradation of EP300 (JQAD1) causes loss of H3K27ac at these enhancers and rapid apoptosis in a CRBN-dependent manner. |
CRISPR KO, PROTAC degrader, ChIP-seq, co-immunoprecipitation, in vivo xenograft |
Cancer discovery |
High |
34772733
|
| 2019 |
AFF1 (a super elongation complex subunit) is site-specifically acetylated by p300; this acetylation reduces AFF1 interaction with other SEC components and impairs P-TEFb-mediated RNA Pol II CTD phosphorylation both in vitro and in vivo. Upon genotoxic stress, p300-mediated AFF1 acetylation correlates with global transcriptional downregulation, and acetylation-defective AFF1 rescues transcription. |
In vitro acetylation and P-TEFb kinase assays, co-immunoprecipitation, mutagenesis, ChIP, genotoxic stress experiments |
Proceedings of the National Academy of Sciences of the United States of America |
High |
31611376
|
| 2020 |
p300 physically interacts with NRF2 and interferes with NRF2-KEAP1 complex formation, thereby increasing NRF2 protein stability and promoting its nuclear localization. The acetyltransferase activity of p300 is indispensable for these stabilizing effects. |
Co-immunoprecipitation, overexpression/knockdown, nuclear fractionation, HAT-dead mutant analysis, cell viability assay |
Biochemical and biophysical research communications |
Medium |
32057361
|
| 2021 |
Short-chain fatty acids propionate and butyrate (but not acetate) activate p300 acetyltransferase by being converted to acyl-CoAs that are used by p300 to catalyze auto-acylation of the autoinhibitory loop, resulting in enzyme activation and global histone acetylation—distinct from HDAC inhibition. |
Quantitative proteomics of histone modifications, in vitro HAT assay, metabolite tracing, genetic/chemical perturbation |
eLife |
High |
34677127
|
| 2022 |
Cryo-EM structures reveal that p300/CBP recognizes histone H4 N-terminal tail acetylation via its bromodomain (and contacts DNA minor grooves outside the pocket), directing the catalytic center to non-H4 histone tails within the same nucleosome. The primary write target after reading H4NTac is H2BNT; H2BNTac promotes H2A-H2B dissociation from the nucleosome. |
Cryo-EM structure, in vitro acetyltransferase assay, nucleosome dissociation assay |
Nature communications |
High |
37460559
|
| 2022 |
The TAZ2 domain of p300 has an autoinhibitory function for HAT activity. Truncation of TAZ2 leads to hyperactive HAT and elevated H3K27ac and H3K18ac. Mechanistically, TAZ2 cooperates with neighboring HAT domains to maintain the active site in a 'closed' state; binding of transcription factors to TAZ2 or TAZ2 truncation induces a conformational opening of the active site. |
HAT activity assay, domain truncation mutagenesis, ChIP-seq, structural modeling, cancer mutation analysis |
Nature communications |
High |
37660055
|
| 2022 |
NUT (in the BRD4-NUT oncoprotein) contains an acidic transcriptional activation domain that binds the TAZ2 domain of p300, allosterically activating p300. NUT-TAZ2 interaction or cancer mutations interfering with TAZ2 autoinhibition activate p300, leading to a self-organizing, acetylation-dependent feed-forward reaction enabling long-range chromatin interactions via bromodomain multivalent acetyl-lysine binding. |
NMR structure, in vitro acetyltransferase assay, mutagenesis, co-immunoprecipitation |
Nature communications |
High |
36522330
|
| 2023 |
EP300 acetylates HSPA5 (GRP78) at K353, and this acetylation reduces HSPA5's ability to inhibit lipid peroxidation, thereby promoting ferroptosis. HDAC6 limits HSPA5 acetylation and subsequent ferroptosis. Genetic or pharmacological inhibition of EP300 increases PDAC cell resistance to ferroptosis. |
Acetylation site mapping, mutagenesis (K353 site), genetic and pharmacological inhibition, ferroptosis assays, co-immunoprecipitation |
Scientific reports |
Medium |
37696842
|
| 2023 |
p300 functions as a writer of histone crotonylation during preimplantation embryo development. P300 depletion causes developmental defects and transcriptome dysregulation. H3K18 crotonylation (H3K18cr), catalyzed by P300, localizes to active promoter regions and activates gene transcription required for embryo development. |
Genetic depletion (microinjection), RNA-seq, ChIP-seq, in vitro crotonylation assay |
Nature communications |
High |
39080296
|
| 2023 |
p300 is an obligate integrator of combinatorial transcription factor inputs for chromatin binding: systematic mutagenesis of all annotated p300 domains in live cells shows that chromatin association depends entirely on combinatorial binding through multiple TF-interaction domains. p300 acetyltransferase activity opposes its chromatin association, and N-terminal TF-interaction domains regulate catalytic activity. |
Single-molecule tracking (live cell imaging), domain mutagenesis, U2OS cells |
Molecular cell |
High |
38159566
|
| 2023 |
HDAC8 deacetylates EP300, causing its enzymatic inactivation. This inactivation increases EP300 binding to Jun-transcriptional sites and decreases binding to MITF-transcriptional sites, altering chromatin accessibility and driving a neural crest-stem cell transcriptional state promoting melanoma brain metastasis. |
ATAC-seq, ChIP-seq, HDAC8 inhibitor treatment, loss-of-function, mass spectrometry |
Nature communications |
Medium |
38030596
|
| 2023 |
EP300 acetylates raptor (mTORC1 component), and nucleus-cytoplasmic shuttling of p300/EP300 regulates mTORC1 activity in response to amino acid or glucose levels. Nutrient deprivation causes AMPK-dependent phosphorylation of p300 at serine 89, promoting its cytoplasm-to-nucleus relocalization, reducing raptor acetylation and mTORC1 activity, and activating autophagy. Nutrient repletion causes PP2A-dependent dephosphorylation of nuclear p300, enabling CRM1-dependent nuclear export and mTORC1 reactivation. In Hutchinson-Gilford progeria syndrome, progerin mislocalizes p300 to the cytoplasm, hyperactivating mTORC1. |
Subcellular fractionation, co-immunoprecipitation, siRNA knockdown, AMPK inhibition, CRM1 inhibition, in vivo mouse tissue analysis, patient cell lines |
Nature cell biology |
High |
38267537
|
| 2024 |
p300 functions as a succinylation writer (succinyl-CoA transferase) for cytoplasmic proteins including glycolytic enzymes. EP300 deletion leads to systemic reduction of lysine succinylation; p300-mediated succinylation of PGK1 promotes glycolysis, and mutation of the succinylated site of PGK1 impairs glycolysis and lactate production in lung cancer cells. |
Succinylome proteomics (SILAC/MS), CRISPR KO of EP300, site mutagenesis, glycolysis/metabolomics assays |
International journal of molecular sciences |
Medium |
38256128
|
| 2019 |
EP300 acetylates FOXO3, and this acetylation promotes lapatinib sensitivity in HER2-positive breast cancer cells. Ectopic expression of wild-type but not acetylation-deficient EP300 increases acetylated-FOXO3 and lapatinib cytotoxicity; SIRT1/6 deacetylate FOXO3, counteracting EP300 activity. |
Ectopic expression, acetylation-deficient mutant, SIRT1/6 siRNA/inhibitor, drug sensitivity assay, ChIP |
Cancers |
Medium |
31357743
|
| 2019 |
p300 catalyzes acetylation of NONO at K198, stabilizing NONO by antagonizing its RNF8-mediated ubiquitination/degradation. NONO stabilizes CRAF and ARAF, reactivating pERK1/2 and promoting BRAF inhibitor resistance in melanoma. ERK1/2 activation feeds back to induce p300, forming a positive feedback loop. |
Co-immunoprecipitation, in vitro acetylation assay, mutagenesis, ubiquitination assay, in vitro/in vivo drug resistance assays |
Oncogene |
Medium |
34017080
|
| 2022 |
p300/CBP sustains Polycomb-group protein occupancy at repressive sites by non-enzymatic functions: CBP stabilizes RNA Pol II at PcG-bound sites and promotes Pol II pausing independently of HAT activity. CBP/Pol II pausing is required for R-loop formation and nucleosome depletion at Polycomb Response Elements. |
ChIP-seq, genetic manipulation in Drosophila and mouse cells, HAT-dead mutant, R-loop detection |
Molecular cell |
Medium |
36206738
|
| 2023 |
EP300 interacts with YAP and ZEB (via its Bromo domain and CBP/p300-HAT domain respectively) and simultaneously binds these factors to induce H3K27 acetylation at the LPCAT3 promoter, activating LPCAT3 transcription and thereby promoting ferroptosis sensitivity in lung adenocarcinoma cells. |
Co-immunoprecipitation, ChIP-qPCR, dual-luciferase reporter, xenograft model, domain interaction mapping |
Antioxidants & redox signaling |
Medium |
37166352
|