From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
KAT2B
Available structures
PDB Ortholog search:
PDBe
RCSB List of PDB id codes
1CM0 ,
1JM4 ,
1N72 ,
1WUG ,
1WUM ,
1ZS5 ,
2RNW ,
2RNX ,
3GG3 ,
4NSQ ,
5FE2 ,
5FE4 ,
5FDZ ,
5FE8 ,
5FE5 ,
5FE1 ,
5FE7 ,
5FE9 ,
5FE3 ,
5FE0 ,
5FE6
Identifiers
Aliases
KAT2B , CAF, P/CAF, PCAF, lysine acetyltransferase 2BExternal IDs
OMIM :
602303
MGI :
1343094
HomoloGene :
20834
GeneCards :
KAT2B
Wikidata
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]
Interactions
PCAF has been shown to
interact with:
BRCA2 ,
[12]
[13]
CTNNB1 ,
[14]
CREBBP ,
[15]
[16]
EVI1 ,
[17]
HNF1A ,
[18]
IRF1 ,
[19]
IRF2 ,
[19]
[20]
KLF13 ,
[21]
Mdm2
[22]
Myc ,
[23]
NCOA1 ,
[24]
POLR2A ,
[16]
RBPJ ,
[25]
TCF3 ,
[26]
TRRAP ,
[23]
[27] and
TWIST1 .
[28]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000114166 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000000708 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b Linares LK, Kiernan R, Triboulet R, Chable-Bessia C, Latreille D, Cuvier O, Lacroix M, Le Cam L, Coux O, Benkirane M (March 2007). "Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2". Nat. Cell Biol . 9 (3): 331–8.
doi :
10.1038/ncb1545 .
PMID
17293853 .
S2CID
205286563 .
^
"Entrez Gene: PCAF p300/CBP-associated factor" .
^ Santos-Rosa H, Valls E, Kouzarides T, Martínez-Balbás M (August 2003).
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PMC
169960 .
PMID
12888487 .
^ Grégoire S, Xiao L, Nie J, Zhang X, Xu M, Li J, Wong J, Seto E, Yang XJ (February 2007).
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^ Chérasse Y, Maurin AC, Chaveroux C, Jousse C, Carraro V, Parry L, Deval C, Chambon C, Fafournoux P, Bruhat A (2007).
"The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP" . Nucleic Acids Res . 35 (17): 5954–65.
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PMC
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PMID
17726049 .
^ Asano Y, Czuwara J, Trojanowska M (November 2007).
"Transforming growth factor-beta regulates DNA binding activity of transcription factor Fli1 by p300/CREB-binding protein-associated factor-dependent acetylation" . J. Biol. Chem . 282 (48): 34672–83.
doi :
10.1074/jbc.M703907200 .
PMID
17884818 .
^ Liu L, Scolnick DM, Trievel RC, Zhang HB, Marmorstein R, Halazonetis TD, Berger SL (February 1999).
"p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage" . Mol. Cell. Biol . 19 (2): 1202–9.
doi :
10.1128/MCB.19.2.1202 .
PMC
116049 .
PMID
9891054 .
^ Lin HR, Ting NS, Qin J, Lee WH (Sep 2003).
"M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex" . J. Biol. Chem . 278 (38): 35979–87.
doi :
10.1074/jbc.M210659200 .
PMID
12815053 .
^ Fuks F, Milner J, Kouzarides T (Nov 1998). "BRCA2 associates with acetyltransferase activity when bound to P/CAF". Oncogene . 17 (19): 2531–4.
doi :
10.1038/sj.onc.1202475 .
PMID
9824164 .
S2CID
9999991 .
^ Ge X, Jin Q, Zhang F, Yan T, Zhai Q (Jan 2009).
"PCAF acetylates {beta}-catenin and improves its stability" . Mol. Biol. Cell . 20 (1): 419–27.
doi :
10.1091/mbc.E08-08-0792 .
PMC
2613091 .
PMID
18987336 .
^ Tini M, Benecke A, Um SJ, Torchia J, Evans RM, Chambon P (Feb 2002).
"Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription" . Mol. Cell . 9 (2): 265–77.
doi :
10.1016/S1097-2765(02)00453-7 .
PMID
11864601 .
^
a
b Cho H, Orphanides G, Sun X, Yang XJ, Ogryzko V, Lees E, Nakatani Y, Reinberg D (Sep 1998).
"A human RNA polymerase II complex containing factors that modify chromatin structure" . Mol. Cell. Biol . 18 (9): 5355–63.
doi :
10.1128/MCB.18.9.5355 .
PMC
109120 .
PMID
9710619 .
^ Chakraborty S, Senyuk V, Sitailo S, Chi Y, Nucifora G (Nov 2001).
"Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles" . J. Biol. Chem . 276 (48): 44936–43.
doi :
10.1074/jbc.M106733200 .
PMID
11568182 .
^ Soutoglou E, Papafotiou G, Katrakili N, Talianidis I (Apr 2000).
"Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins" . J. Biol. Chem . 275 (17): 12515–20.
doi :
10.1074/jbc.275.17.12515 .
PMID
10777539 .
^
a
b Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K (Mar 1999).
"The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness" . Mol. Cell. Biol . 19 (3): 1810–20.
doi :
10.1128/MCB.19.3.1810 .
PMC
83974 .
PMID
10022868 .
^ Masumi A, Ozato K (Jun 2001).
"Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment" . J. Biol. Chem . 276 (24): 20973–80.
doi :
10.1074/jbc.M101707200 .
PMID
11304541 .
^ Song CZ, Keller K, Murata K, Asano H,
Stamatoyannopoulos G (Mar 2002).
"Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2" . J. Biol. Chem . 277 (9): 7029–36.
doi :
10.1074/jbc.M108826200 .
PMC
2808425 .
PMID
11748222 .
^ Jin Y, Zeng SX, Dai MS, Yang XJ, Lu H (Aug 2002).
"MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation" . J. Biol. Chem . 277 (34): 30838–43.
doi :
10.1074/jbc.M204078200 .
PMID
12068014 .
^
a
b Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E (May 2003).
"c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation" . J. Biol. Chem . 278 (22): 20405–12.
doi :
10.1074/jbc.M211795200 .
PMC
4031917 .
PMID
12660246 .
^ Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY,
Tsai MJ , O'Malley BW (Sep 1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature . 389 (6647): 194–8.
Bibcode :
1997Natur.389..194S .
doi :
10.1038/38304 .
PMID
9296499 .
S2CID
4404530 .
^ Kurooka H, Honjo T (Jun 2000).
"Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5" . J. Biol. Chem . 275 (22): 17211–20.
doi :
10.1074/jbc.M000909200 .
PMID
10747963 .
^ Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (Jan 2003).
"Regulation of E2A activities by histone acetyltransferases in B lymphocyte development" . J. Biol. Chem . 278 (4): 2370–6.
doi :
10.1074/jbc.M211464200 .
PMID
12435739 .
^ Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM (Aug 2001).
"The p400 complex is an essential E1A transformation target" . Cell . 106 (3): 297–307.
doi :
10.1016/s0092-8674(01)00450-0 .
PMID
11509179 .
S2CID
15634637 .
^ Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (Feb 1999).
"Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A" . Cell . 96 (3): 405–13.
doi :
10.1016/S0092-8674(00)80553-X .
PMID
10025406 .
S2CID
15808193 .
External links
Further reading
Marcello A, Zoppé M, Giacca M (2002).
"Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator" . IUBMB Life . 51 (3): 175–81.
doi :
10.1080/152165401753544241 .
PMID
11547919 .
S2CID
10931640 .
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 .
ISBN
978-0-470-86263-6 .
PMID
15171254 .
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 .
PMID
15183343 .
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.
PMID
16035254 .
Hetzer C, Dormeyer W, Schnölzer M, Ott M (2006).
"Decoding Tat: the biology of HIV Tat posttranslational modifications" . Microbes Infect . 7 (13): 1364–9.
doi :
10.1016/j.micinf.2005.06.003 .
PMID
16046164 .
Peruzzi F (2006).
"The multiple functions of HIV-1 Tat: proliferation versus apoptosis" . Front. Biosci . 11 : 708–17.
doi :
10.2741/1829 .
PMID
16146763 .
Stevens M, De Clercq E, Balzarini J (2007).
"The regulation of HIV-1 transcription: molecular targets for chemotherapeutic intervention" . Med Res Rev . 26 (5): 595–625.
doi :
10.1002/med.20081 .
PMC
7168390 .
PMID
16838299 .
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 .
PMID
17168834 .
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 .
PMID
1602151 .
Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y (1996). "A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A". Nature . 382 (6589): 319–24.
Bibcode :
1996Natur.382..319Y .
doi :
10.1038/382319a0 .
PMID
8684459 .
S2CID
4328685 .
Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1997).
"The transcriptional coactivators p300 and CBP are histone acetyltransferases" . Cell . 87 (5): 953–9.
doi :
10.1016/S0092-8674(00)82001-2 .
PMID
8945521 .
S2CID
2624456 .
Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, O'Malley BW (1997).
"Steroid receptor induction of gene transcription: a two-step model" . Proc. Natl. Acad. Sci. U.S.A . 94 (15): 7879–84.
Bibcode :
1997PNAS...94.7879J .
doi :
10.1073/pnas.94.15.7879 .
PMC
21523 .
PMID
9223281 .
Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (1997).
"Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300" . Cell . 90 (3): 569–80.
doi :
10.1016/S0092-8674(00)80516-4 .
PMID
9267036 .
S2CID
15284825 .
Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW (1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature . 389 (6647): 194–8.
Bibcode :
1997Natur.389..194S .
doi :
10.1038/38304 .
PMID
9296499 .
S2CID
4404530 .
Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (1997).
"TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1" . J. Biol. Chem . 272 (44): 27629–34.
doi :
10.1074/jbc.272.44.27629 .
PMID
9346901 .
Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG (1998). "Transcription factor-specific requirements for coactivators and their acetyltransferase functions". Science . 279 (5351): 703–7.
Bibcode :
1998Sci...279..703K .
doi :
10.1126/science.279.5351.703 .
PMID
9445475 .
Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y, Levrero M (1998).
"Differential roles of p300 and PCAF acetyltransferases in muscle differentiation" . Mol. Cell . 1 (1): 35–45.
doi :
10.1016/S1097-2765(00)80005-2 .
PMID
9659901 .
Ogryzko VV, Kotani T, Zhang X, Schiltz RL, Howard T, Yang XJ, Howard BH, Qin J, Nakatani Y (1998).
"Histone-like TAFs within the PCAF histone acetylase complex" . Cell . 94 (1): 35–44.
doi :
10.1016/S0092-8674(00)81219-2 .
PMID
9674425 .
S2CID
18942972 .
Randhawa GS, Bell DW, Testa JR, Feinberg AP (1998).
"Identification and mapping of human histone acetylation modifier gene homologues" . Genomics . 51 (2): 262–9.
doi :
10.1006/geno.1998.5370 .
PMID
9722949 .
Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatani Y, Jeang KT (1998).
"Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat" . J. Biol. Chem . 273 (38): 24898–905.
doi :
10.1074/jbc.273.38.24898 .
PMID
9733796 .
PDB gallery
1cm0 : CRYSTAL STRUCTURE OF THE PCAF/COENZYME-A COMPLEX
1jm4 : NMR Structure of P/CAF Bromodomain in Complex with HIV-1 Tat Peptide
1n72 : Structure and Ligand of a Histone Acetyltransferase Bromodomain
1wug : complex structure of PCAF bromodomain with small chemical ligand NP1
1wum : Complex structure of PCAF bromodomain with small chemical ligand NP2
1zs5 : Structure-based evaluation of selective and non-selective small molecules that block HIV-1 TAT and PCAF association
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .