PCAF

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 2B
External IDs	OMIM: 602303; MGI: 1343094; HomoloGene: 20834; GeneCards: KAT2B; OMA:KAT2B - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p24.3 Start 20,040,446 bp [1] End 20,154,404 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17 C|17 27.86 cM Start 53,873,889 bp [2] End 53,979,748 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in external globus pallidus trabecular bone buccal mucosa cell corpus callosum Achilles tendon subthalamic nucleus pars reticulata amniotic fluid Skeletal muscle tissue of rectus abdominis pars compacta Top expressed in retinal pigment epithelium nasal epithelium olfactory epithelium Epithelium of choroid plexus iris seminal vesicula vestibular membrane of cochlear duct gastrula extensor digitorum longus muscle ankle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription coregulator activity protein binding acyltransferase activity histone acetyltransferase activity cyclin-dependent protein serine/threonine kinase inhibitor activity protein kinase binding chromatin binding lysine N-acetyltransferase activity, acting on acetyl phosphate as donor transcription coactivator activity transcription factor binding histone deacetylase binding acetyltransferase activity protein-containing complex binding peptide-lysine-N-acetyltransferase activity diamine N-acetyltransferase activity Cellular component I band nucleoplasm histone acetyltransferase complex A band actomyosin kinetochore nucleus cytoplasm centrosome microtubule organizing center cytoskeleton protein-containing complex Biological process Notch signaling pathway regulation of protein ADP-ribosylation epigenetic maintenance of chromatin in transcription-competent conformation chromatin remodeling regulation of transcription, DNA-templated negative regulation of cyclin-dependent protein serine/threonine kinase activity rhythmic process N-terminal peptidyl-lysine acetylation transcription, DNA-templated positive regulation of transcription, DNA-templated histone acetylation histone H3 acetylation cellular response to insulin stimulus histone H3-K9 acetylation cell cycle transcription initiation from RNA polymerase II promoter viral process peptidyl-lysine acetylation negative regulation of cell population proliferation positive regulation of transcription by RNA polymerase II internal peptidyl-lysine acetylation regulation of megakaryocyte differentiation protein acetylation positive regulation of transcription of Notch receptor target heart development positive regulation of Notch signaling pathway negative regulation of centriole replication limb development protein deubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8850 18519 Ensembl ENSG00000114166 ENSMUSG00000000708 UniProt Q92831 Q9JHD1 RefSeq (mRNA) NM_003884 NM_001190846 NM_020005 RefSeq (protein) NP_003875 NP_001177775 NP_064389 Location (UCSC) Chr 3: 20.04 – 20.15 Mb Chr 17: 53.87 – 53.98 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

• Transcription coregulator
• Acetyltransferase

References

1. GRCh38: Ensembl release 89: ENSG00000114166 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000000708 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: PCAF p300/CBP-associated factor".
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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

• PCAF protein, human at the U.S. 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. 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.

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