P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
and
transcriptional coactivator associated with
p53.
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 ubiquitin ...
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 and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...
s and
nucleosome
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone, histone proteins and resembles thread wrapped around a bobbin, spool. The 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
Histone deacetylase 3 is an enzyme encoded by the ''HDAC3'' gene in both humans and mice.
Function
Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein comp ...
, 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 and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...
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
''BRCA2'' and BRCA2 () are human genes and their protein products, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associate ...
,
*
CTNNB1,
*
CREBBP,
*
EVI1,
*
HNF1A,
*
IRF1,
*
IRF2,
[
* ]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 gene Su(H), Suppressor of Hairless. Its promoter ...
,TCF3
Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) e ...
,
See also
* Transcription coregulator
* Acetyltransferase
References
External links
*
*
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
{{NLM content
Gene expression
Transcription coregulators