CBP / p300 (CREBBP / EP300 family)

Division of labor: This page is the family-level overview for the KAT3 (CREBBP/EP300) paralog pair, covering shared domain architecture, catalytic mechanism, the substrate landscape relevant to aging, and the family-wide pharmacology. ep300 is the canonical home for p300-specific findings (autophagy regulation, Pietrocola 2015 spermidine mechanism, Yao 1998 KO phenotype); those claims are cross-referenced here, not restated. No separate atomic page yet exists for CREBBP; CREBBP-specific findings are covered here.

CBP (CREB-binding protein, encoded by CREBBP) and p300 (E1A-binding protein, encoded by EP300) are the two members of the KAT3 family of lysine acetyltransferases — large (~265 kDa) nuclear scaffold proteins that function simultaneously as catalytic writers of histone and non-histone acetylation marks and as physical bridging co-activators between sequence-specific transcription factors and the RNA Pol II machinery. Together they acetylate hundreds of substrates including p53, foxo1/foxo3/foxo4, pgc-1alpha, NF-κB (see nf-kb), and all four core histones; their H3K27ac mark is the primary epigenomic indicator of active enhancers genome-wide. Multiple aging-relevant pathways — p53-pathway, FOXO/sirtuin axis, autophagy suppression — converge on CBP/p300 acetyltransferase activity. The family is pharmacologically tractable via selective HAT-domain inhibitors (A-485, inobrodib/CCS1477) now in clinical-oncology trials.

Members

Member	UniProt	NCBI Gene	HGNC	Length	MW	Atomic page
CREBBP (CBP, KAT3A)	Q92793	1387	2348	2,442 aa	~265 kDa	covered here
EP300 (p300, KAT3B)	Q09472	2033	3373	2,414 aa	~265 kDa	ep300 (verified-partial)

Both entries are Swiss-Prot (manually reviewed). Overall sequence identity between CREBBP and EP300 is ~63%; identity in the catalytic HAT domain is ~75% [UniProt Q92793, Q09472 — accessed 2026-05-05]. Both are one-to-one orthologs in mouse (Crebbp, Ep300), with high sequence conservation throughout.

Domain architecture

CBP and EP300 share the same modular domain organization (N→C); residue numbers given for CREBBP (2,442 aa) followed by approximate EP300 equivalents where they differ meaningfully [UniProt Q92793; see ep300 for EP300-specific residue table]:

Domain	CREBBP residues (approx.)	Function
TAZ1 (zinc-finger)	~347–433	Binds HIF1A, CITED2, and other transactivators bearing the LPQL/VXXLL motif
KIX domain	~587–666	Binds phospho-CREB, MYB, and other activation domains; site of Menke-Hennekam missense mutations
Bromodomain (BRD)	~1,085–1,192	Reads acetyl-lysine on histones; required for chromatin recruitment; clinical BRD-inhibitor target
HAT domain (KAT3A)	~1,323–1,700	Catalytic acetyltransferase; acetylates histones and non-histone substrates; also performs crotonylation, butyrylation, propionylation, lactylation on histone lysines
ZZ zinc-finger	~1,702–1,750	Conserved with EP300; function not fully characterized
TAZ2 zinc-finger	~1,765–1,846	Binds p53 (TAD2), nuclear hormone receptors, and other TF activation domains
IBiD / NCBD	~2,059–2,117	Binds IRF-3, MYB, NCOA2; disordered region involved in innate immune gene activation

The bromodomain and HAT domain are the two principal drug targets. The BRD reads the HAT’s own acetylation marks as well as histone marks, creating a positive-feedback loop that stabilizes CBP/p300 at active enhancers.

Catalysis: autoacetylation activates the HAT domain

CBP and EP300 belong to the GNAT superfamily of acetyltransferases but have a structurally distinct HAT domain. A critical regulatory feature is autoacetylation of an activation loop within the HAT domain: in EP300, Thompson et al. 2004 showed that the activation loop (residues ~1536–1572) must be autoacetylated for full HAT activity ¹. Karanam et al. 2006 extended this by kinetic and mass-spectrometric mapping of autoacetylation sites within the p300 HAT domain, showing that multiple lysines within the activation loop are sequentially autoacetylated in a mechanism-based fashion, and that this autoacetylation is kinetically coupled to substrate acetylation ². The biological consequence is that p300/CBP HAT activity is sensitive to acetyl-CoA availability (the acetyl donor) — connecting their activity to cellular metabolic state. needs-replication — whether autoacetylation is the primary regulatory switch in vivo (vs co-activator recruitment, phosphorylation, or allosteric effects) is not fully resolved; most evidence is from purified protein in vitro.

Dimension	Status
Mechanism conserved in humans?	yes — Thompson 2004 and Karanam 2006 used human p300 protein
Phenotype tested in humans?	not directly; downstream substrate acetylation is the phenotypic readout

Substrate landscape — aging-relevant targets

CBP/p300 acetylate hundreds of non-histone proteins. The table below summarizes the most aging-relevant substrates, with the key lysine sites and primary citation.

Substrate	Key acetylation sites	Effect of acetylation	Deacetylase	Primary source
p53 K370/K372/K373/K381/K382	K382 (principal)	Stabilizes p53; displaces MDM2 from K382-overlapping ubiquitination site; activates sequence-specific DNA binding	sirt1 (K382); HDAC1	Gu & Roeder 1997 ³
foxo3 / foxo1 / foxo4	Multiple (K242/K245/K262 on FOXO3)	Modulates FOXO transcriptional output; p300 is the writer; SIRT1 is the dominant eraser in the deacetylation direction	sirt1	Brunet 2004 ⁴
pgc-1alpha	13 sites: K77/K144/K183/K253/K270/K277/K320/K346/K412/K441/K450/K757/K778	Inhibits PGC-1α transcriptional co-activator activity on gluconeogenic genes; SIRT1 deacetylation restores activity. Writer identity not established by Rodgers 2005 — p300/CBP as acetyltransferase is inferred from the family’s known substrate scope, not demonstrated in this paper.	sirt1	Rodgers 2005 ⁵ needs-replication
NF-κB p65 (RelA)	K310 (principal); K221/K218	K310ac enhances NF-κB transcriptional activity; K218/K221ac promotes nuclear export / dissociation from DNA	SIRT1/HDAC3	Chen 2002 ⁶
Histone H3K18, H3K27	H3K27ac marks active enhancers	H3K27ac distinguishes active enhancers from poised; marks cis-regulatory elements genome-wide	HDAC1/2	Heintzman 2009 ⁷
ATG5, ATG7, ATG8/LC3, ATG12	Multiple cytoplasmic Lys	Acetylation suppresses autophagy initiation; p300 knockdown induces autophagy	— (spermidine competes for HAT active site)	Lee & Finkel 2009 ⁸

p53 acetylation — the canonical substrate

Gu and Roeder 1997 established that p300 directly acetylates the C-terminal regulatory domain of p53 — specifically the C-terminal 30 amino acids (residues 363–393) — in a biochemically purified system and in cells ³. Using a synthetic C-terminal peptide (residues 364–389) and amino-terminal peptide sequencing, the paper identified five preferentially acetylated lysines: K370, K372, K373, K381, and K382 (K382 most strongly labeled; K386 was explicitly shown to be unacetylated relative to background). Acetylation of these five lysines markedly stimulates p53 sequence-specific DNA binding in vitro (~20- to 30-fold over unmodified p53). The proposed mechanism is conformational: p53’s C-terminal tail interacts with the central DNA-binding core in an auto-inhibitory fashion; acetylation neutralizes the positive charges in the tail, disrupting this tail–core interaction and allowing the DNA-binding domain to adopt an active conformation. The MDM2-competition mechanism (K382ac competing with ubiquitination) is attributed to later work not directly demonstrated in Gu 1997. This is the founding mechanistic link between CBP/p300 HAT activity and the p53-pathway. See p53 for the canonical p53 aging-antagonistic-pleiotropy discussion.

FOXO acetylation — the SIRT1 reciprocity axis

Brunet et al. 2004 showed that SIRT1 deacetylates FOXO3a (at K242, K245, K262) in response to oxidative stress, modulating its transcriptional output — specifically increasing expression of stress-resistance genes (GADD45) while decreasing pro-apoptotic targets ⁴. Because the reciprocal modification (acetylation) is the CBP/p300 “write” step in the FOXO regulatory cycle, this paper establishes CBP/p300 as the upstream writer whose activity is antagonized by SIRT1. The sirtuin / FOXO axis, heavily studied in deregulated-nutrient-sensing and longevity contexts, is thus directly upstream and downstream of CBP/p300 activity. See foxo3 for a full FOXO aging discussion.

Dimension	Status
Pathway conserved in humans?	yes — study used human cell lines; FOXO3 and CBP/p300 are highly conserved
Phenotype conserved in humans?	partial — FOXO3 polymorphisms associate with human longevity; CBP/p300 role in human FOXO biology not directly tested in aging context
Replicated in humans?	no (aging endpoint) needs-human-replication

PGC-1α acetylation — metabolic aging axis

Rodgers et al. 2005 demonstrated that SIRT1 deacetylates PGC-1α at 13 specific lysines (K77, K144, K183, K253, K270, K277, K320, K346, K412, K441, K450, K757, K778 — mapped by tandem mass spectrometry in 293T cells) in an NAD⁺-dependent manner, and that SIRT1-mediated deacetylation activates PGC-1α’s co-activator function for gluconeogenic gene programs (PEPCK, G6Pase) in fasted mouse liver ⁵. The paper shows that acetylation of PGC-1α suppresses its transcriptional activity (nicotinamide-treated cells with hyperacetylated PGC-1α showed 24-fold repression of HNF4α-driven transcription). Importantly, Rodgers 2005 does not identify the acetyltransferase responsible for PGC-1α acetylation — the paper’s focus is exclusively on SIRT1 as the eraser. The attribution of CBP/p300 as the writer is inferred from their broad substrate scope but is not demonstrated in this paper. needs-replication — CBP/p300 as the PGC-1α acetyltransferase requires direct experimental attribution. Rodgers 2005 used 4-week-old C57Bl/6 mice (fasted 24 h); generalization to aged animals and to human aging requires independent study.

NF-κB (RelA) acetylation — inflammation axis

Chen et al. 2002 showed that CBP/p300 acetylate RelA (NF-κB p65) at K310 and K218/K221 — distinct sites with distinct functional consequences: K310ac is required for full NF-κB transcriptional activation; K218/K221ac promotes nuclear export ⁶. Because chronic NF-κB activation is a driver of chronic-inflammation (inflammaging, see epigenetic-alterations), CBP/p300 HAT activity is a node linking acetylation to the inflammatory hallmarks of aging. SIRT1 deacetylates K310 to attenuate NF-κB signaling, providing a further SIRT1/CBP-p300 antagonism. needs-replication — whether this axis is aging-altered in human tissue is not directly established.

H3K27ac — the active enhancer mark

Heintzman et al. 2009 performed ChIP-chip profiling of histone modifications across cell types and showed that active enhancers (versus gene bodies, promoters, or poised enhancers) are specifically marked by H3K27ac and H3K4me1 — and co-occupy with CBP/p300 ⁷. This established H3K27ac as the primary epigenomic indicator of CBP/p300 occupancy at active cis-regulatory elements. The age-associated drift in the enhancer landscape — shifts in H3K27ac patterns at homeostasis-relevant loci — is hypothesized to contribute to the epigenetic-alterations hallmark, though the causal contribution of CBP/p300 activity changes specifically is not established. no-mechanism

Autophagy substrate acetylation — link to ep300

Lee and Finkel 2009 showed that p300 (EP300) acetylates ATG proteins (ATG5, ATG7, ATG8/LC3, ATG12) in the cytoplasm, suppressing autophagy initiation; p300 knockdown or spermidine-mediated competitive inhibition de-represses autophagic flux ⁸. This is the primary aging-relevant function detailed on ep300 (verified-partial); the mechanism is canonical on that page. The relevant point at the family level: the substrate acetylation here is attributed primarily to EP300 based on siRNA specificity in Pietrocola 2015 (see ep300), not to CREBBP — a rare documented functional divergence between the two paralogs.

Aging relevance

CBP/p300 as a hub integrating stress, nutrient, and damage signals

The convergence of p53, FOXO, PGC-1α, and NF-κB all on CBP/p300 as an upstream writer means that the HAT activity of this family sits at the intersection of the major aging-relevant signaling axes. When CBP/p300 HAT activity is high (nutrient-replete, low-stress state), it tends to:

Acetylate and thereby modulate FOXO target selectivity
Acetylate and activate NF-κB
Acetylate and suppress PGC-1α
Acetylate and suppress ATG proteins (EP300-specific)

SIRT1 deacetylation reverses most of these — creating a CBP/p300 ↔ SIRT1 push/pull at multiple aging-relevant substrates. Caloric restriction and NAD+ repletion shift the balance toward SIRT1 activity and away from CBP/p300 dominance. Whether age-associated changes in CBP/p300 protein levels, HAT activity, or substrate access are causal contributors to aging (rather than downstream consequences of other changes) is not established. no-mechanism

Spermidine and autophagy — EP300-specific (cross-reference to ep300)

The spermidine → EP300 inhibition → autophagy induction mechanism is covered fully on ep300 and cross-referenced here to avoid duplication. The key family-level note: Pietrocola 2015’s siRNA screen distinguished EP300 as the relevant paralog for autophagy suppression (CBP/CREBBP knockdown did not phenocopy in that assay), making this the clearest documented functional divergence between the two paralogs. See spermidine and ep300 for primary citations and quantitative claims.

CBP/p300 haploinsufficiency and development — the gene-dosage context

Yao et al. 1998 showed that Ep300 homozygous null mice die embryonically (E9.5–E11.5) and that compound haploinsufficiency of both Crebbp and Ep300 (double heterozygotes) is also embryonic lethal, demonstrating that the combined gene dose of CBP and p300 must exceed a threshold for normal development ⁹. This gene-dosage sensitivity is directly relevant to disease (Rubinstein-Taybi syndrome; see below) and sets the safety boundary for pharmacological HAT inhibition — systemic suppression of both paralogs below the critical threshold is expected to be harmful. See ep300 for full details on the Yao 1998 data (verified on that page).

Disease: Rubinstein-Taybi syndrome (RSTS)

Rubinstein-Taybi syndrome is an autosomal-dominant developmental disorder caused by heterozygous loss-of-function mutations in either CREBBP (→ RSTS type 1) or EP300 (→ RSTS type 2). Clinical features shared across subtypes: intellectual disability, broad thumbs and toes, characteristic craniofacial dysmorphology, and postnatal growth retardation.

RSTS1 (CREBBP): Established by Petrij et al. 1995, who identified chromosome 16p13.3 deletions and point mutations in CREBBP as causative. The paper examined 16 patients by protein truncation test (PTT), finding truncated CBP proteins in 2, and also characterized chromosomal rearrangements/microdeletions in the 16p13.3 region ¹⁰. CREBBP mutations account for ~55–60% of genetically confirmed RSTS cases (per Roelfsema 2005 and later series).
RSTS2 (EP300): Roelfsema et al. 2005 screened 92 RSTS patients and found 36 CREBBP and 3 EP300 mutations, establishing EP300 as a second causative locus ¹¹. The CREBBP:EP300 mutation ratio of ~12:1 in that cohort is consistent with later larger series reporting ~55–60% CREBBP and ~8–10% EP300. Full details on the EP300 RSTS data are on ep300 (verified against Roelfsema 2005 PDF).

The unequal disease frequencies (RSTS1 >> RSTS2) likely reflect both mutation ascertainment bias and potentially different phenotypic penetrance rather than different functional importance of the two paralogs.

Pharmacology

A-485 — selective p300/CBP HAT inhibitor

Lasko et al. 2017 described A-485 — a potent, selective p300/CBP HAT inhibitor with IC₅₀ ~60 nM against p300 in biochemical assays and ~5 nM in cellular activity assays — as a candidate anti-cancer agent ¹². A-485 shows high selectivity over PCAF, GCN5, and other HAT family members. It selectively kills androgen receptor-driven prostate cancer cells and hematological cancer cells by depleting H3K27ac and suppressing AR/MYC target genes. No published aging-specific studies. In autophagy biology, A-485 is a higher-potency successor to C646 for interrogating CBP/p300 HAT functions. needs-replication — A-485 has not been tested in longevity studies in any organism.

CCS1477 / Inobrodib — clinical-stage BRD inhibitor

CCS1477 (inobrodib) targets the bromodomain (not the HAT domain) of CBP/p300. Currently in Phase 1/2 trials for castration-resistant prostate cancer and hematological malignancies (e.g., NCT04068597). As a BRD inhibitor, it prevents CBP/p300 from reading acetyl-lysine at enhancers, disrupting transcriptional co-activation downstream of BRD occupancy, without directly inhibiting HAT catalysis. Clinical proof-of-concept that CBP/p300 is pharmacologically tractable in humans is accumulating, though aging-specific endpoints are not yet studied. long-term-unknown

C646 — EP300-selective HAT inhibitor (tool compound)

C646 (IC₅₀ ~1.6 µM vs EP300 HAT) is a well-validated research tool used in the autophagy-regulation studies described on ep300. It remains a tool compound only; not in clinical development.

SIRT1 activators — indirect modulation of CBP/p300 substrates

Compounds activating SIRT1 (e.g., resveratrol, SRT2104, NMN-replete NAD+) effectively oppose CBP/p300-mediated acetylation at shared substrates (p53 K382, FOXO3, PGC-1α). This indirect pharmacology places the SIRT1-activator class (see sirt1) as functional CBP/p300 substrate antagonists at specific sites. The distinction matters: SIRT1 activation does not reduce global CBP/p300 activity or H3K27ac patterns at enhancers; it opposes specific substrate acetylation events.

Limitations and gaps

CBP vs p300 attribution: The majority of cell biology uses “p300/CBP” collectively and cannot attribute specific effects to one paralog. Genetic knockouts, isoform-selective inhibitors, or targeted point mutations are required to dissociate their contributions. Most claims on this page apply to both; see ep300 for EP300-specific mechanistic dissection. contradictory-evidence
Aging causality: Whether CBP/p300 HAT activity causally changes with organismal aging (rising, falling, or redistributing substrate acetylation) is not established in primary aging studies with genetic manipulation of the family. Age-associated observations are largely correlative or inferred from substrates (FOXO acetylation, H3K27ac drift). no-mechanism
CREBBP-specific aging studies: GenAge-human and GenAge-models do not currently list CREBBP (as of 2026-05-04). No primary study directly manipulates Crebbp in a lifespan or healthspan context. All lifespan-relevant data comes from shared substrates or from EP300 specifically. needs-replication — a dedicated page for CREBBP aging phenotypes will require new primary evidence.
Autoacetylation in vivo: The Thompson 2004 / Karanam 2006 autoacetylation mechanism is established with purified protein; whether fluctuations in intracellular acetyl-CoA levels modulate CBP/p300 HAT activity through this mechanism in a physiologically meaningful way in aged tissue is untested. no-mechanism
H3K27ac drift with age (causal role): CBP/p300’s role in writing H3K27ac positions them as suspects in age-associated enhancer remodeling, but causal evidence that CBP/p300 redistributes its enhancer occupancy as a cause (rather than consequence) of cellular aging is lacking. no-mechanism
Long-term HAT inhibitor safety: Systemic chronic CBP/p300 HAT inhibition would be expected to have broad effects on tissue homeostasis, immune function, and haematopoiesis given the family’s ubiquitous co-activator role. Long-term safety in healthy adults is unknown. long-term-unknown

Cross-references

ep300 — paralog; canonical page for p300-specific findings (autophagy suppression, Pietrocola 2015, Yao 1998 KO data, spermidine mechanism)
p53 — substrate; CBP/p300 acetylates p53 K382; interactor on p53.md (verified)
p53-pathway — pathway with CBP/p300 as a key p53-stabilizing co-activator
foxo3 — substrate; CBP/p300 acetylates FOXO3; antagonized by sirt1
foxo1 — substrate; same FOXO acetylation axis
pgc-1alpha — substrate; CBP/p300 acetylation suppresses PGC-1α; SIRT1 deacetylation activates it
sirt1 — major functional antagonist; deacetylates multiple CBP/p300 substrates (p53, FOXO3, PGC-1α, NF-κB)
nf-kb — substrate (RelA K310); CBP/p300 activates NF-κB-driven inflammatory transcription
autophagy — suppressed by EP300-mediated ATG protein acetylation (see ep300)
spermidine — polyamine that competitively inhibits EP300 HAT activity; de-represses autophagy
deregulated-nutrient-sensing — hallmark; FOXO and PGC-1α axes
epigenetic-alterations — hallmark; H3K27ac enhancer landscape
loss-of-proteostasis — hallmark; linked via autophagy suppression
chronic-inflammation — linked via NF-κB RelA acetylation
caloric-restriction — CR shifts SIRT1/CBP-p300 balance toward deacetylation at key substrates

Footnotes

doi:10.1038/nsmb740 · Thompson PR et al. (2004) “Regulation of the p300 HAT domain via a novel activation loop” · Nat Struct Mol Biol 11(4):308–315 · in-vitro (biochemical, purified protein) · model: recombinant human p300 HAT domain · 417 citations · not OA; no local PDF (archive: not_oa) no-fulltext-access ↩
doi:10.1074/jbc.M608813200 · Karanam B et al. (2006) “Kinetic and Mass Spectrometric Analysis of p300 Histone Acetyltransferase Domain Autoacetylation” · J Biol Chem 281(52):40292–40301 · in-vitro (biochemical, mass spectrometry) · model: purified recombinant human p300 HAT domain · 91 citations · archive: pending download no-fulltext-access ↩
doi:10.1016/s0092-8674(00)80521-8 · Gu W & Roeder RG (1997) “Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain” · Cell 90(4):595–606 · in-vitro (biochemical + cell culture) · n=N/A (biochemical assays) · model: purified human p300 protein; Saos-2 and H1299 cells · 2,543 citations · local PDF: ↩ ↩²
doi:10.1126/science.1094637 · Brunet A et al. (2004) “Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase” · Science 303(5666):2011–2015 · in-vitro (cell culture + biochemical) · model: human 293T cells; mouse neuronal cells; IP-kinase assay · 3,185 citations · archive: not OA; no local PDF no-fulltext-access ↩ ↩²
doi:10.1038/nature03354 · Rodgers JT et al. (2005) “Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1” · Nature 434(7029):113–118 · in-vivo + in-vitro · model: 4-week-old C57Bl/6 mouse liver (fasted 24 h / refed 24 h); Fao rat hepatocytes; 293T cells · primary finding: SIRT1 is the NAD⁺-dependent deacetylase for PGC-1α (13 acetylated lysines mapped by mass spec); acetyltransferase writer for PGC-1α NOT identified in this paper · 3,055 citations · local PDF: ↩ ↩²
doi:10.1093/emboj/cdf660 · Chen L et al. (2002) “Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB” · EMBO J 21(23):6539–6548 · in-vitro (cell culture, biochemical) · model: HeLa and Jurkat cells; CBP and p300 co-transfections · 801 citations · archive: pending download; OA bronze no-fulltext-access ↩ ↩²
doi:10.1038/nature07829 · Heintzman ND et al. (2009) “Histone modifications at human enhancers reflect global cell-type-specific gene expression” · Nature 459(7243):108–112 · in-vitro (ChIP-chip in human cell lines) · model: 5 human cell lines (HeLa, GM06690, K562, ES, BMP4-induced ES); ChIP-chip for H3K4me1, H3K4me3, H3K27ac + p300 ChIP; H3K27ac + p300 co-occupancy marks active enhancers in cell-type-specific manner; genome-wide prediction of >55,000 enhancers · 2,518 citations · local PDF: ↩ ↩²
doi:10.1074/jbc.M807135200 · Lee IH & Finkel T (2009) “Regulation of Autophagy by the p300 Acetyltransferase” · J Biol Chem 284(10):6322–6328 · in-vitro (cell culture) · model: HeLa cells · n=3 independent experiments · 261 citations · local PDF: (verified on ep300) ↩ ↩²
doi:10.1016/s0092-8674(00)81165-4 · Yao TP et al. (1998) “Gene Dosage-Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300” · Cell 93(3):361–372 · in-vivo (mouse, germline KO) · model: Ep300+/− and Ep300−/− on 129/Sv and 129×BL6 backgrounds · 1,001 citations · local PDF verified on ep300 ↩
doi:10.1038/376348a0 · Petrij F et al. (1995) “Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP” · Nature 376(6538):348–351 · observational (human genetics) · n=16 RSTS patients examined by protein truncation test (PTT); truncated proteins found in 2 patients; additional patients with chromosomal rearrangements/deletions also described; 16p13.3 as CREBBP locus established · 1,215 citations · local PDF: ↩
doi:10.1086/429130 · Roelfsema JH et al. (2005) “Genetic Heterogeneity in Rubinstein-Taybi Syndrome: Mutations in Both the CBP and EP300 Genes Cause Disease” · Am J Hum Genet 76(4):572–580 · observational (human genetics) · n=92 RSTS patients; 36 CREBBP + 3 EP300 mutations found · 467 citations · local PDF: (verified on ep300) ↩
doi:10.1038/nature24028 · Lasko LM et al. (2017) “Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours” · Nature 550(7674):128–132 · in-vitro + in-vivo (cell lines + mouse xenograft) · model: human prostate cancer and AML cell lines; mouse xenograft; IC₅₀ ~60 nM biochemical / ~5 nM cellular · 803 citations · archive: pending download; OA (PMC6050590) no-fulltext-access — IC₅₀ values not verified against full text; download pending ↩

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