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Pcaf

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Title: Pcaf  
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Subject: Histone acetylation and deacetylation, CREB-binding protein, TCF3, HNF1A, IRF2
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Pcaf

K(lysine) acetyltransferase 2B
PDB rendering based on 1cm0.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; CAF; P/CAF; PCAF
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
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.

Contents

  • Structure 1
  • Function 2
  • Regulation 3
  • Protein interactions 4
  • Targets 5
  • Interactions 6
  • See also 7
  • References 8
  • External links 9
  • Further reading 10

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:

See also

References

  1. ^ 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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  9. ^ Fuks F, Milner J, Kouzarides T (Nov 1998). "BRCA2 associates with acetyltransferase activity when bound to P/CAF". Oncogene 17 (19): 2531–4.  
  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.  
  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.  
  12. ^ 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.  
  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.  
  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.  
  15. ^ 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.  
  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.  
  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.  
  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.  
  19. ^ 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.  
  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.  
  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.  
  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.  
  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.  
  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.  

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.  
  • 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.  
  • 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.  
  • 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.  
  • Hetzer C, Dormeyer W, Schnölzer M, Ott M (2006). "Decoding Tat: the biology of HIV Tat posttranslational modifications". Microbes Infect. 7 (13): 1364–9.  
  • Peruzzi F (2006). "The multiple functions of HIV-1 Tat: proliferation versus apoptosis". Front. Biosci. 11: 708–17.  
  • 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.  
  • 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.  
  • Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Randhawa GS, Bell DW, Testa JR, Feinberg AP (1998). "Identification and mapping of human histone acetylation modifier gene homologues". Genomics 51 (2): 262–9.  
  • 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.  

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

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