PCAF

K(lysine) acetyltransferase 2B
PDB rendering based on 1cm0.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1CM0​, 1JM4​, 1N72​, 1WUG​, 1WUM​, 1ZS5​, 2RNW​, 2RNX​, 3GG3​, 4NSQ​
Identifiers
Symbols	KAT2B ; CAF; P/CAF; PCAF
External IDs	OMIM: 602303 MGI: 1343094 HomoloGene: 20834 ChEMBL: 5500 GeneCards: KAT2B Gene
EC number	2.3.1.48
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • chromatin binding • transcription cofactor activity • transcription coactivator activity • histone acetyltransferase activity • lysine N-acetyltransferase activity, acting on acetyl phosphate as donor • cyclin-dependent protein serine/threonine kinase inhibitor activity • protein binding • transcription factor binding • acetyltransferase activity • protein kinase binding • protein complex binding • histone acetyltransferase binding • histone deacetylase binding Cellular component • PCAF complex • kinetochore • nuclear chromatin • nucleus • nucleoplasm • Ada2/Gcn5/Ada3 transcription activator complex • cytosol • A band • I band • actomyosin Biological process • chromatin organization • chromatin remodeling • transcription from RNA polymerase I promoter • transcription initiation from RNA polymerase I promoter • transcription initiation from RNA polymerase II promoter • protein acetylation • cell cycle arrest • Notch signaling pathway • memory • negative regulation of cell proliferation • gene expression • regulation of protein ADP-ribosylation • positive regulation of neuron projection development • viral process • N-terminal peptidyl-lysine acetylation • internal peptidyl-lysine acetylation • peptidyl-lysine acetylation • cellular response to insulin stimulus • cellular response to oxidative stress • positive regulation of chromatin binding • positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter • histone H3 acetylation • histone H3-K9 acetylation • negative regulation of cyclin-dependent protein serine/threonine kinase activity • positive regulation of vasodilation • positive regulation of transcription from RNA polymerase II promoter • rhythmic process • cellular response to parathyroid hormone stimulus • positive regulation of histone H3-K14 acetylation • positive regulation of histone H3-K9 acetylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8850	18519
Ensembl	ENSG00000114166	ENSMUSG00000000708
UniProt	Q92831	Q9JHD1
RefSeq (mRNA)	NM_003884	NM_001190846
RefSeq (protein)	NP_003875	NP_001177775
Location (UCSC)	Chr 3: 20.04 – 20.15 Mb	Chr 17: 53.57 – 53.67 Mb
PubMed search

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.^[1]

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.^[2]

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.^[3] PCAF interacts with and is deacetylated by HDAC3, leading to a reduction in PCAF acetyltransferase activity and cytoplasmic localisation.^[4]

Protein interactions

PCAF forms complexes with numerous proteins that guide its activity. For example PCAF is recruited by ATF^[5] 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,^[6] p53^[7] 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.^[1]

Interactions

PCAF has been shown to interact with:

• BRCA2,^[8][9]
• CTNNB1,^[10]
• CREBBP,^[11][12]
• EVI1,^[13]
• HNF1A,^[14]
• IRF1,^[15]
• IRF2,^[15][16]
• KLF13,^[17]
• Mdm2^[18]
• Myc,^[19]
• NCOA1,^[20]
• POLR2A,^[12]
• RBPJ,^[21]
• TCF3,^[22]
• TRRAP,^[19][23] and
• TWIST1.^[24]

See also

• Transcription coregulator
• Acetyltransferase

References

1. 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.
2. "Entrez Gene: PCAF p300/CBP-associated factor".
3. Santos-Rosa H, Valls E, Kouzarides T, Martínez-Balbás M (August 2003). "Mechanisms of P/CAF auto-acetylation". Nucleic Acids Res. 31 (15): 4285–92. doi:10.1093/nar/gkg655. PMC 169960. PMID 12888487.
4. Grégoire S, Xiao L, Nie J, Zhang X, Xu M, Li J, Wong J, Seto E, Yang XJ (February 2007). "Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2". Mol. Cell. Biol. 27 (4): 1280–95. doi:10.1128/MCB.00882-06. PMC 1800729. PMID 17158926.
5. 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. doi:10.1093/nar/gkm642. PMC 2034469. PMID 17726049.
6. 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.
7. 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. PMC 116049. PMID 9891054.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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. PMC 109120. PMID 9710619.
13. 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.
14. 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.
15. 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. PMC 83974. PMID 10022868.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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. doi:10.1038/38304. PMID 9296499.
21. 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.
22. 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.
23. 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.
24. 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.

External links

• PCAF protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C105

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.
• 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.". Novartis Found. Symp. Novartis Foundation Symposia 259: 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. 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. doi:10.1038/382319a0. PMID 8684459.
• 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.
• 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. 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.
• 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. doi:10.1038/38304. PMID 9296499.
• 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. 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.
• 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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.