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 ba ...

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 CBP may refer to: Business parks * Cebu Business Park, a central business district in Cebu City, Philippines * Changi Business Park, an eco-friendly industrial park in Singapore * Chiswick Business Park, a business park in Gunnersbury, West London ...

and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including

c-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...

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 Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring ...

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 The Bureau of Alcohol, Tobacco, Firearms and Explosives (BATFE), commonly referred to as the ATF, is a domestic law enforcement agency within the United States Department of Justice. Its responsibilities include the investigation and preven ...

to acetylate

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 Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the ''FLI1'' gene, which is a proto-oncogene. Function Fli-1 is a member of the ETS transcription fa ...

, 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

BRCA2 ''BRCA2'' and BRCA2 () are a human gene and its protein product, 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 associated) ...

, *

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 Interferon regulatory factor 2 is a protein that in humans is encoded by the ''IRF2'' gene. Function IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhib ...

, * 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 The nuclear receptor coactivator 1 (''NCOA1'') is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by ...

, *

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 gene Suppressor of Hairless. Its promoter region ...

, *

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) ex ...

, *

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 Twist-related protein 1 (TWIST1) also known as class A basic helix–loop–helix protein 38 (bHLHa38) is a basic helix-loop-helix transcription factor that in humans is encoded by the ''TWIST1'' gene. Function Basic helix-loop-helix (bHLH) tr ...

References

External links

* *