P300 coactivator proteins. Medical search. Frequent questions

The transcriptional coactivator p300/CBP (CREBBP) is a histone acetyltransferase (HAT) that regulates gene expression by acetylating histones and other transcription factors. (umassmed.edu)
The p300-CBP coactivator family in humans is composed of two closely related transcriptional co-activating proteins (or coactivators): p300 (also called EP300 or E1A binding protein p300) CBP (also known as CREB-binding protein or CREBBP) Both p300 and CBP interact with numerous transcription factors and act to increase the expression of their target genes. (wikipedia.org)
CREB binding protein (CBP, CREBBP) and its paralog p300 (EP300) constitute the KAT3 family of HATs in mammals, which has mostly unique sequence identity compared to other HAT families. (aging-us.com)
The locus of Rubinstein-Taybi syndrome is located on band 16p13.3, which includes a gene encoding a binding protein for cyclic adenosine monophosphate-response element binding protein (CBP) ( CREBBP or CBP gene) that is responsible for the phenotype of Rubinstein-Taybi syndrome. (medscape.com)
The EP300 gene on band 22q13 encodes a protein, p300, that is highly similar to CREBBP. (medscape.com)

p300 and CBP are thought to increase gene expression in three ways: by relaxing the chromatin structure at the gene promoter through their intrinsic histone acetyltransferase (HAT) activity. (wikipedia.org)
Work done by Heintzman and colleagues showed that 70% of the p300 binding occurs in open chromatin regions as seen by the association with DNase I hypersensitive sites. (wikipedia.org)
Current models of transcription regulation have also shown the involvement of higher-order transcriptional coactivators, proteins that nucleate around DNA sequence-specific transcription factors, enhancing transcription of the target gene by interacting with components of the basal transcriptional apparatus and by enabling chromatin remodeling. (nih.gov)
Coactivator proteins such as SRC1 and CBP/p300 are recruited by agonist bound receptors and promote initiation of transcription by remodelling the chromatin structure while coactivators such as the PPAR binding protein (PBP) and TRAP220 interact directly with the transcriptional machinery. (sigmaaldrich.com)
Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. (embl-heidelberg.de)
Chakravarti's laboratory identifies and characterizes the role of chromatin signal transducer proteins including the recently identified INHAT proteins in gene regulation. (northwestern.edu)
The lab is also characterizing members of a novel THAP domain protein family regarding their roles in gene regulation, chromatin signaling, cell growth and differentiation and cancer. (northwestern.edu)
These studies are important because they identify these proteins as key transducers of chromatin signaling during cell cycle progression. (northwestern.edu)
The canonical nucleosome is a fundamental unit of chromatin and consists of a protein octamer of two molecules each of histone H2A, H2B, H3 and H4, wrapped by 147 bp of genomic DNA. (aging-us.com)
Similarly, the recruitment of protein acetyltransferases positively correlates with histone hyperacetylation at active genes as shown by genome-wide chromatin immunoprecipitation (ChIP-Seq) studies of CBP and p300 in human T cells [ 3 ]. (aging-us.com)
Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. (ox.ac.uk)
Both genes are highly conserved, and their proteins are thought to have 2 functions: (1) formation of a bridge or scaffold between the DNA-binding transcription factors and the RNA polymerase II complex and (2) serving as histone acetyltransferases that open the chromatin structure, a process essential for gene expression. (medscape.com)

CBP and EP300 are ubiquitously expressed homologous proteins that act as transcriptional co-activators. (medscape.com)

This modification is PKA mediated, and promotes the interaction of the KID domain of CREB with the KIX domain of CBP or p300 and enhances transcription of CREB target genes, including genes that aid gluconeogenesis. (wikipedia.org)
This directly demonstrates the role that the tertiary regulators, CBP or p300, play in mediating EpRE activation of phase II genes, and also implicates the involvement of secondary, p160 family coactivators. (nih.gov)
Nuclear hormone receptors are ligand-dependent intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences following activation by the appropriate ligand. (thermofisher.com)
We, in a dogma changing study demonstrated that key cell cycle genes are regulated by HCFC1 cofactor recruitment not by the E2F proteins but by a THAP11-ZNF143 transcriptional complex. (northwestern.edu)
Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk. (biomedcentral.com)
Cataloging and testing of coding variants in coactivator and corepressor genes should continue and may serve as a valuable resource for investigations of other hormone-related phenotypes, such as inter-individual response to hormonal therapies used for cancer treatment and prevention. (biomedcentral.com)
Cellular response to estrogens is mediated through estrogen receptors (ERα and ERβ), which upon binding to ligand and DNA hormone response elements, recruit coactivator and corepressor proteins that regulate the expression of steroid hormone target genes. (biomedcentral.com)
In this study, we systematically screened the coding exons of steroid hormone receptor coactivator and corepressor genes in a multiethnic panel of women with breast cancer in an attempt to identify and catalogue potentially functional coding polymorphisms that may serve as genetic markers of breast cancer risk. (biomedcentral.com)
Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. (e-enm.org)

This family contains the fungal KAT11 protein (previously known as RTT109) which is required for H3K56 acetylation. (embl.de)
Acetylation regulates many diverse functions, including DNA recognition, protein-protein interaction and protein stability. (embl-heidelberg.de)
Is histone acetylation the most important physiological function for CBP and p300? (aging-us.com)
Although studies in yeast show that many histone mutations cause modest or specific phenotypes, similar studies are impractical in mammals and it remains uncertain if histone acetylation is the primary physiological function for CBP/p300. (aging-us.com)
Analysis of CBP and p300 mutant mouse fibroblasts reveals CBP/p300 are together chiefly responsible for the global acetylation of histone H3 residues K18 and K27, and contribute to other locus-specific histone acetylation events. (aging-us.com)
CBP/p300 can also be important for transcription, but the recruitment of CBP/p300 and their associated histone acetylation marks do not absolutely correlate with a requirement for gene activation. (aging-us.com)
Chemically synthesized histone H3 protein, corresponding to residues within 1-135 of human histone H3, acetylation at K64. (ks-vpeptide.com)
We will use overexpression and dominant-negative approaches to investigate if ADA complex functions as a coactivator for p53, and determine if coactivator function relates to histone acetylation on p53 target gene promoters and/or p53 acetylation. (grantome.com)
In addition to histone acetylation, CBP also acetylates various transcription factors, including the tumor suppressor protein p53, to enhance sequence-specific DNA binding. (novusbio.com)
Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. (ox.ac.uk)

TFIID, TBP and TFIIH) and transcriptional co-activators (e.g., p300, P/CAF) bind to p53 [426]. (achrinhibitor.com)

A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. (childrensmercy.org)
The CBP (CREB-binding protein) is a histone acetyltransferase and transcriptional coactivator that regulates RNA polymerase II transcription. (novusbio.com)
Inhibition of the histone acetyltransferase activity of CREB-binding protein (CBP)/p300 blocked the induction of COX-2 by PMA. (johnshopkins.edu)

Several disease-associated mutations can also be readily accounted for by the p300 HAT structure. (umassmed.edu)
Mutations in CBP, and to a lesser extent p300, are the cause of Rubinstein-Taybi Syndrome, which is characterized by severe mental retardation. (wikipedia.org)
These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of CBP or p300 protein by half. (wikipedia.org)
Some mutations lead to the production of a very short, nonfunctional version of the CBP or p300 protein, while others prevent one copy of the gene from making any protein at all. (wikipedia.org)
Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low-affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations. (elifesciences.org)
Nonetheless, CBP and p300 mutations in humans and mice show that these coactivators have important roles in development, physiology, and disease, possibly because CBP and p300 act as network "hubs" with more than 400 described protein interaction partners. (aging-us.com)

Here we report that antidiabetic thiazolidinediones (TZDs) and other ligands for the nuclear receptor PPARγ dramatically upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by facilitating the exchange of coactivators for corepressors on the OLR1 gene in cultured mouse adipocytes. (jci.org)
The binding of ligand triggers a series of events which result in conformational changes involving recruitment of coactivators and dissociation of corepressors. (sigmaaldrich.com)
11 ] The relative recruitment of coactivators versus corepressors for a given ligand (e.g. estradiol vs tamoxifen) is tissue specific and may account for agonist vs. antagonist activity of the same ligand in different tissues. (biomedcentral.com)

Protein lysine acetyltransferases (HATs or PATs) acetylate histones and other proteins, and are principally modeled as transcriptional coactivators. (aging-us.com)

This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. (utsouthwestern.edu)

The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53. (wikipedia.org)
The transactivation function of p53 requires accessory protein complexes, the coactivators, such as the p300/CBP family. (grantome.com)

We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. (elifesciences.org)
Secondly, our effort will stimulate future research on further characterization of all THAP domain proteins. (northwestern.edu)

In addition p300 and CBP each contain a protein or histone acetyltransferase (PAT/HAT) domain and a bromodomain that binds acetylated lysines and a PHD finger motif with unknown function. (wikipedia.org)
In some proteins, the classical bromodomain has diverged to such an extent that parts of the region are either missing or contain an insertion (e.g., mammalian protein HRX, Caenorhabditis elegans hypothetical protein ZK783.4, yeast protein YTA7). (embl-heidelberg.de)
Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). (embl-heidelberg.de)

Moreover, we found that the same anti-MafK antibody that blocked induction of the EpRE-regulated GFP gene completely ablated the gel-shift complex that we hypothesize contains an Nrf2:Maf dimer, ARE-binding protein-1, and CBP or p300. (nih.gov)
By Western blot, this antibody detects an ~56 kDa protein representing PPAR gamma 2 from NIH-3T3 cell lysate. (thermofisher.com)

EGR-1 (Early growth response protein 1) also known as ZNF268 (zinc finger protein 268) or NGFI-A (nerve growth factor-induced protein A) is a protein that in humans is encoded by the EGR1 gene . (wikipedia.org)

This family also incorporates the p300/CBP histone acetyltransferase domain which has different catalytic properties and cofactor regulation to KAT11 (PMID:18568037). (embl.de)
Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog ofmetazoan p300/CBP. (embl.de)
Following a best-candidate approach to identify such a partner, we demonstrated through NMR-monitored titrations and glutathione S-transferase pulldown assays that the OST domain binds to the CH1 and CH3 domains of the co-activator histone acetyltransferase CBP/p300. (ubc.ca)
Citation: Ding Z, Cao J, Shen Y, Zou Y, Yang X, Zhou W, Guo Q and Huang C (2018) Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury. (vinomis.com)
In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. (vinomis.com)
Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. (vinomis.com)
Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair. (vinomis.com)

A greater understanding of the mechanism of transcriptional regulation by nuclear receptors has lead to the identification of multiple accessory proteins that bind to the nuclear receptors in a ligand-dependent manner. (sigmaaldrich.com)

Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. (elifesciences.org)
However, a group of proteins called 'intrinsically disordered proteins' are flexible in their shape and lack a stable three-dimensional structure. (elifesciences.org)
analyzed the amino acid sequences of two specific intrinsically disordered proteins from different organisms to reconstruct the versions of the proteins that were likely found in their common ancestors 450-600 million years ago. (elifesciences.org)
Since these intrinsically disordered regions, which are conformationally dynamic and do not adopt stable secondary or tertiary structures, are often essential for mediating the phase transition of proteins 9 , it is therefore of interest to consider if the C-terminus of IRS-1 is involved in phase separation and to further delineate such implications upon insulin/IGF signaling. (nature.com)

The specific order of amino acids in a protein determines its shape and structure, which in turn controls what the protein can do. (elifesciences.org)
The human EGR-1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5 kDa , and the gene is located on the chromosome 5 . (wikipedia.org)

Using biochemical, molecular and cellular analyses, we demonstrated that histone H3 serine 10 phosphorylation functions as a module that promotes release of key cellular proteins such as SRp20, and heterochromatin protein HP1. (northwestern.edu)
Due to the fact p53 is such a wide-range cellular regulator, numerous proteins can bind to p53 to modify its function, dynamics and stability [41]. (achrinhibitor.com)

NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. (hmdb.ca)

We highlight the importance of protein degradation and/or conformational inactivation for buffering to appear. (biomedcentral.com)

p300 regulates transcription by directly binding to transcription factors (see external reference for explanatory image). (wikipedia.org)
Here, we hypothesized that multiple transcriptional regulators, including: (i) a primary Nrf2-Maf heterodimer, (ii) a proposed secondary, EpRE-specific, p160 family coactivator, ARE-binding protein-1, and (iii) a tertiary coactivator, CBP/p300, nucleate to form a complex at the EpRE that regulates transcription of the dependent gene. (nih.gov)

Both contain five protein interaction domains: the nuclear receptor interaction domain (RID), the KIX domain (CREB and MYB interaction domain), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). (wikipedia.org)
This interaction is managed by one or more of the p300 domains: the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). (wikipedia.org)
They have also found some correlation between p300 and RNAPII binding at enhancers, which can be explained by the physical interaction with promoters or by enhancer RNAs. (wikipedia.org)
a corresponding decrease in the interaction between CBP/p300 and c-Jun was observed. (johnshopkins.edu)

Yet, these proteins play important roles in many processes that require the protein to interact with a number of other proteins. (elifesciences.org)
Insulin receptor substrate (IRS) proteins play essential roles in mediating insulin/IGF signaling by recruiting a series of downstream effectors 23 . (nature.com)

The nuclear receptor corepressor (N-CoR) or silencing mediator of retinoid and thyroid receptors (SMRT) proteins bind and mediate repression of transcription by the unliganded receptors. (sigmaaldrich.com)

also known as NCOA3 or AIB1) is a member of the multifunctional p160/SRC family of coactivators, which also includes SRC-1 and SRC-2. (frontiersin.org)

Ultimately, we concluded that substantial transactivating function of p53 to the p21 upstream promoter and subsequent development repression requirements the binding of TAD1 domain of p53 towards the middle region of TLP.TLP-binding capacity of p53 and TLP-mediated cell deathCells expressing a substantial degree of p21 proteins undergo development arrest and occasional cell death. (achrinhibitor.com)

It is a nuclear protein and functions as a transcriptional regulator. (wikipedia.org)

Here we describe a high-resolution X-ray crystal structure of a semi-synthetic heterodimeric p300 HAT domain in complex with a bi-substrate inhibitor, Lys-CoA. (umassmed.edu)

Materials and Methods: The expression of COM-1 mRNA was examined using a quantitative polymerase chain reaction (PCR) technique together with immunohistochemistry to examine expression and distribution of the COM-1 protein in human colorectal carcinoma and matched normal colorectal mucosa. (iiarjournals.org)

This structure shows that p300/CBP is a distant cousin of other structurally characterized HATs, but reveals several novel features that explain the broad substrate specificity and preference for nearby basic residues. (umassmed.edu)
The Rtt109 structure reveals noteworthyhomology to the metazoan p300/CBP HAT domain but exhibits functional divergence, including atypical catalytic properties and mode of cofactor regulation. (embl.de)
Thestructure reveals a buried autoacetylated lysine residue that we show is alsoacetylated in the Rtt109 protein purified from yeast cells. (embl.de)

Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB β). (nature.com)

Enhancer regions, which regulate gene transcription, are known to be bound by p300 and CBP, and ChIP-seq for these proteins has been used to predict enhancers. (wikipedia.org)
EGR-1 has also been found to regulate the expression of VAMP2 (a protein important for synaptic exocytosis ). (wikipedia.org)

The protein encoded by this gene belongs to the EGR family of Cys 2 His 2 -type zinc finger proteins. (wikipedia.org)

Tumours at advanced stage express COM-1 protein to a lesser extent than their early-stage counterparts. (iiarjournals.org)
DNA sequence) influences the extent to which CBP and p300 are necessary for transcription. (aging-us.com)

p300-CBP Transcription Factors" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (childrensmercy.org)

It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. (utsouthwestern.edu)

Furthermore, they have described that most p300 binding (75%) occurs far away from transcription start sites (TSSs) and these binding sites are also associated with enhancer regions as seen by H3K4me1 enrichment. (wikipedia.org)

Sequence alignments, enzymology experiments and inhibitor studies on p300/CBP have led to contradictory results about its catalytic mechanism and its structural relation to the Gcn5/PCAF and MYST HATs. (umassmed.edu)

Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxia-inducible factor 1-α (HIF-1α) expression, glycolysis-related gene (GRG) expression and pro-cancer activities, such as cell migration, cell viability and tumor-promoting cytokine secretion. (bvsalud.org)

In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. (embl-heidelberg.de)

COM-1, candidate of metastasis-1, otherwise known as p8, is a primarily nuclear protein initially discovered within the last decade by the differential display of cDNA from breast cancer metastases within the brains of athymic nude rats. (iiarjournals.org)

These studies pave the way for new epigenetic therapies involving modulation of p300/CBP HAT activity. (umassmed.edu)

Some G proteins stimulate adenylate cyclase that results in elevation of cAMP. (wikipedia.org)

Based on this structure and accompanying biochemical data, we propose that p300/CBP uses an unusual 'hit-and-run' (Theorell-Chance) catalytic mechanism that is distinct from other characterized HATs. (umassmed.edu)
Relevant to the role of CBP/p300 as HATs, hyperacetylation of histone N-terminal tail lysines correlates strongly with active transcription [ 2 ]. (aging-us.com)

One of Chakravarti's major research interests is to determine the mechanisms of steroid hormone and vitamin signaling with special emphasis on the role of the nuclear hormone receptor co-regulatory proteins in gene transcription. (northwestern.edu)
Such imbalances stem from under- or over-expression of a subunit of a complex consequent to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein. (biomedcentral.com)
To gain insight into the biochemical bases of the effects of stoichiometric imbalances, we explore the consequences of under- or over-expression of a subunit of a complex due, for instance, to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein in a diploid organism. (biomedcentral.com)
Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. (ox.ac.uk)

EGR-1 recruits the TET1 protein that initiates a pathway of DNA demethylation . (wikipedia.org)

They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. (ox.ac.uk)

There are 3024 KAT11 domains in 3017 proteins in SMART's nrdb database. (embl.de)
There are 52668 BROMO domains in 38864 proteins in SMART's nrdb database. (embl-heidelberg.de)

They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. (childrensmercy.org)
The primary function of the mammary gland is to provide nutrition for the young in the form of milk protein and fat. (biologists.com)

Finally, we will quantify p53-mediated cell cycle arrest and apoptotic responses to DNA damage to assess the role of ADA complex versus p300/CBP in regulating p53-mediated DNA damage response, using overexpression as well as dominant-negative strategies. (grantome.com)

Anatomy22

Organisms8

Diseases2

Chemicals and Drugs147

Analytical, Diagnostic and Therapeutic Techniques and Equipment19

Phenomena and Processes58

Information Science3

CREBBP5

Chromatin12

EP3001

Genes9

Acetylation10

Transcriptional co-activators1

CREB-BINDING3

Mutations6

Corepressors3

Histones1

Adenovirus1

Transactivation2

Characterization2

Bromodomain3

Antibody2

Humans1

Acetyltransferase7

Accessory proteins1

Intrinsically disordered4

Amino acids2

Cellular2

Domain-containi1

Conformational1

Regulates transcription2

Interaction4

Roles2

Mediate1

P1601

Repression1

Regulator1

Heterodimeric1

Polymerase1

Reveals3

Mice1

Regulate2

Family1

Extent2

MeSH1

Specifically to phosphorylated1

Enhancer1

Inhibitor1

Factor1

Interact1

Nuclear protein1

Modulation1

Stimulate1

HATs2

Regulatory4

Recruits1

Sequence-specific1

Domains2

Function2

Versus1