P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
and
transcriptional coactivator associated with
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
.
Structure
Several domains of PCAF can act independently or in unison to enable its functions. PCAF has separate
acetyltransferase and
E3 ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquiti ...
domains as well as a
bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination.
Function
CBP and
p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including
c-jun and the adenoviral oncoprotein E1A. The protein encoded by the PCAF gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has
histone acetyl transferase activity with core
histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
s and
nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.
Regulation
The
acetyltransferase activity and cellular location of PCAF are regulated through acetylation of PCAF itself. PCAF may be autoacetylated (acetylated by itself) or by
p300. Acetylation leads to migration to the nucleus and enhances its acetyltransferase activity.
PCAF interacts with and is deacetylated by
HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.
Protein interactions
PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by
ATF to acetylate
histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
s and promote transcription of ATF4 target genes.
Targets
There are various protein targets of PCAF's acetyltransferase activity including transcription factors such as
Fli1,
p53
and numerous histone residues.
Hdm2, itself a ubiquitin ligase that targets p53, has also been demonstrated to be a target of the ubiquitin-ligase activity of PCAF.
Interactions
PCAF has been shown to
interact with:
*
BRCA2,
*
CTNNB1
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcriptio ...
,
*
CREBBP
Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intri ...
,
*
EVI1
MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the ''MECOM'' gene. EVI ...
,
*
HNF1A
HNF1 homeobox A (hepatocyte nuclear factor 1 homeobox A), also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is high ...
,
*
IRF1
Interferon regulatory factor 1 is a protein that in humans is encoded by the ''IRF1'' gene.
Function
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially descr ...
,
*
IRF2,
* KLF13,
* Mdm2
* Myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' ( MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes refe ...
,
* NCOA1,
* POLR2A
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that in humans is encoded by the ''POLR2A'' gene.
Function
This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing m ...
,[
* ]RBPJ
Recombination signal binding protein for immunoglobulin kappa J region is a protein that in humans is encoded by the ''RBPJ'' gene.
RBPJ also known as CBF1, is the human homolog for the Drosophila
''Drosophila'' () is a genus of flies, belo ...
,
* TCF3,
* TRRAP
Transformation/transcription domain-associated protein, also known as TRRAP, is a protein that in humans is encoded by the ''TRRAP'' gene. TRRAP belongs to the phosphatidylinositol 3-kinase-related kinase protein family.
Function
TRRAP is an ad ...
, and
* TWIST1.
See also
* Transcription coregulator
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription ar ...
* Acetyltransferase
References
External links
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Further reading
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{{NLM content
Gene expression
Transcription coregulators