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 A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA p ...

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 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 la ...

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 ar ...

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 proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

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, 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 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 transcript ...

, * CREBBP, * EVI1, *

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 hig ...

, *

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, * NCOA1, * POLR2A, * RBPJ, *

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 ...

, * TRRAP, and * TWIST1.

References

External links

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