P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human
gene 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 domains as well as a
bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination.[5]
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
histones and
nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.[6]
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.[7] PCAF interacts with and is deacetylated by
HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.[8]
Protein interactions
PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by
ATF[9] to acetylate
histones and promote transcription of ATF4 target genes.
Targets
There are various protein targets of PCAF's acetyltransferase activity including transcription factors such as
Fli1,[10] p53[11] 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.[5]
Ott M, Dorr A, Hetzer-Egger C, Kaehlcke K, Schnolzer M, Henklein P, Cole P, Zhou MM, Verdin E (2004). "Tat Acetylation: A Regulatory Switch between Early and Late Phases in HIV Transcription Elongation". Reversible Protein Acetylation. Novartis Foundation Symposia. Vol. 259. pp. 182–93, discussion 193–6, 223–5.
doi:
10.1002/0470862637.ch13.
ISBN978-0-470-86263-6.
PMID15171254.
Liou LY, Herrmann CH, Rice AP (2005). "HIV-1 infection and regulation of Tat function in macrophages". Int. J. Biochem. Cell Biol. 36 (9): 1767–75.
doi:
10.1016/j.biocel.2004.02.018.
PMID15183343.
Gibellini D, Vitone F, Schiavone P, Re MC (2005). "HIV-1 tat protein and cell proliferation and survival: a brief review". New Microbiol. 28 (2): 95–109.
PMID16035254.
Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets. 7 (12): 1595–606.
doi:
10.2174/138945006779025338.
PMID17168834.
Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20.
doi:
10.1016/S0163-4453(05)80037-4.
PMID1602151.
P300/CBP-associated factor (PCAF), also known as K(lysine) acetyltransferase 2B (KAT2B), is a human
gene 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 domains as well as a
bromodomain for interaction with other proteins. PCAF also possesses sites for its own acetylation and ubiquitination.[5]
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
histones and
nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.[6]
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.[7] PCAF interacts with and is deacetylated by
HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.[8]
Protein interactions
PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by
ATF[9] to acetylate
histones and promote transcription of ATF4 target genes.
Targets
There are various protein targets of PCAF's acetyltransferase activity including transcription factors such as
Fli1,[10] p53[11] 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.[5]
Ott M, Dorr A, Hetzer-Egger C, Kaehlcke K, Schnolzer M, Henklein P, Cole P, Zhou MM, Verdin E (2004). "Tat Acetylation: A Regulatory Switch between Early and Late Phases in HIV Transcription Elongation". Reversible Protein Acetylation. Novartis Foundation Symposia. Vol. 259. pp. 182–93, discussion 193–6, 223–5.
doi:
10.1002/0470862637.ch13.
ISBN978-0-470-86263-6.
PMID15171254.
Liou LY, Herrmann CH, Rice AP (2005). "HIV-1 infection and regulation of Tat function in macrophages". Int. J. Biochem. Cell Biol. 36 (9): 1767–75.
doi:
10.1016/j.biocel.2004.02.018.
PMID15183343.
Gibellini D, Vitone F, Schiavone P, Re MC (2005). "HIV-1 tat protein and cell proliferation and survival: a brief review". New Microbiol. 28 (2): 95–109.
PMID16035254.
Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets. 7 (12): 1595–606.
doi:
10.2174/138945006779025338.
PMID17168834.
Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20.
doi:
10.1016/S0163-4453(05)80037-4.
PMID1602151.