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Title: Ep300  
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Subject: CREB-binding protein, P53, P300, ING4, MAF (gene)
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E1A binding protein p300
PDB rendering based on 1f81.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; KAT3B; RSTS2; p300
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

E1A binding protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene.[1] This protein regulates the activity of many genes in tissues throughout the body. It plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.

The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2.

EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16.


  • Function 1
  • Mechanism 2
  • Clinical significance 3
  • Interactions 4
  • References 5
  • Further reading 6
  • External links 7


This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein.

The protein functions as histone acetyltransferase[2] that regulates transcription via chromatin remodeling, and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein.

This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in the stimulation of hypoxia-induced genes such as VEGF.[3]


The p300 protein carries out its function by activating transcription. To be specific, p300 connects transcription factors, which are proteins that start the transcription process, with the complex of proteins that carry out transcription in the cell's nucleus. On the basis of this function, p300 is called a transcriptional coactivator. The p300 interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions (TAZ1/CH1 and TAZ2/CH3) and the interferon response binding domain (IBiD). The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.[4]

Clinical significance

Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein-Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.

Chromosomal rearrangements involving chromosome 22 have rarely been associated with certain types of cancer. These rearrangements, called translocations, disrupt the region of chromosome 22 that contains the EP300 gene. For example, researchers have found a translocation between chromosomes 8 and 22 in several people with a cancer of blood cells called acute myeloid leukemia (AML). Another translocation, involving chromosomes 11 and 22, has been found in a small number of people who have undergone cancer treatment. This chromosomal change is associated with the development of AML following chemotherapy for other forms of cancer.

Mutations in the EP300 gene have been identified in several other types of cancer. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. Somatic mutations in the EP300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast, and pancreas. Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form.


EP300 has been shown to interact with:


  1. ^ Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM (April 1994). "Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor". Genes Dev. 8 (8): 869–84.  
  2. ^ Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1996). "The transcriptional coactivators p300 and CBP are histone acetyltransferases". Cell 87 (5): 953–9.  
  3. ^ "Entrez Gene: EP300". 
  4. ^ Teufel DP, Freund SM, Bycroft M, Fersht AR (April 2007). "Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53". PNAS 104 (17): 7009–7014.  
  5. ^ Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW (October 1999). "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". J. Biol. Chem. 274 (40): 28491–6.  
  6. ^ a b Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (January 2002). "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Res. 62 (1): 141–51.  
  7. ^ Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM (February 2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5.  
  8. ^ a b Hussain MA, Habener JF (October 1999). "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator". J. Biol. Chem. 274 (41): 28950–7.  
  9. ^ Mink S, Haenig B, Klempnauer KH (November 1997). "Interaction and functional collaboration of p300 and C/EBPbeta". Mol. Cell. Biol. 17 (11): 6609–17.  
  10. ^ Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ, Shioda T (March 2000). "The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors". J. Biol. Chem. 275 (12): 8825–34.  
  11. ^ Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM (January 1999). "Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1". Genes Dev. 13 (1): 64–75.  
  12. ^ a b Bragança J, Eloranta JJ, Bamforth SD, Ibbitt JC, Hurst HC, Bhattacharya S (May 2003). "Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2". J. Biol. Chem. 278 (18): 16021–9.  
  13. ^ Bragança J, Swingler T, Marques FI, Jones T, Eloranta JJ, Hurst HC, Shioda T, Bhattacharya S (March 2002). "Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2". J. Biol. Chem. 277 (10): 8559–65.  
  14. ^ Glenn DJ, Maurer RA (December 1999). "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression". J. Biol. Chem. 274 (51): 36159–67.  
  15. ^ Rossow KL, Janknecht R (January 2003). "Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300". Oncogene 22 (1): 151–6.  
  16. ^ Yamamoto N, Yamamoto S, Inagaki F, Kawaichi M, Fukamizu A, Kishi N, Matsuno K, Nakamura K, Weinmaster G, Okano H, Nakafuku M (November 2001). "Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor". J. Biol. Chem. 276 (48): 45031–40.  
  17. ^ Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, Gan J, DeCaprio JA, Adams PD, Kaelin WG (December 2000). "Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle". Mol. Cell. Biol. 20 (23): 8889–902.  
  18. ^ MacLellan WR, Xiao G, Abdellatif M, Schneider MD (December 2000). "A novel Rb- and p300-binding protein inhibits transactivation by MyoD". Mol. Cell. Biol. 20 (23): 8903–15.  
  19. ^ Li QJ, Yang SH, Maeda Y, Sladek FM, Sharrocks AD, Martins-Green M (January 2003). "MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300". EMBO J. 22 (2): 281–91.  
  20. ^ a b Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, Debril MB, Miard S, Auwerx J (December 2002). "The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation". Dev. Cell 3 (6): 903–10.  
  21. ^ Kang YK, Guermah M, Yuan CX, Roeder RG (March 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2642–7.  
  22. ^ Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hübscher U, Hottiger MO (June 2001). "Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300". Mol. Cell 7 (6): 1221–31.  
  23. ^ Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ (July 2000). "AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins". J. Virol. 74 (13): 5872–9.  
  24. ^ Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (February 2002). "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch". Science 295 (5556): 858–61.  
  25. ^ Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ (April 2002). "Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5367–72.  
  26. ^ Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y (May 2002). "Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter". Diabetes 51 (5): 1409–18.  
  27. ^ Martens JH, Verlaan M, Kalkhoven E, Dorsman JC, Zantema A (April 2002). "Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes". Mol. Cell. Biol. 22 (8): 2598–606.  
  28. ^ a b Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC (May 2003). "p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity". Cancer Res. 63 (10): 2373–8.  
  29. ^ Masumi A, Ozato K (June 2001). "Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment". J. Biol. Chem. 276 (24): 20973–80.  
  30. ^ Hecht A, Stemmler MP (February 2003). "Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4". J. Biol. Chem. 278 (6): 3776–85.  
  31. ^ a b Chen Q, Dowhan DH, Liang D, Moore DD, Overbeek PA (July 2002). "CREB-binding protein/p300 co-activation of crystallin gene expression". J. Biol. Chem. 277 (27): 24081–9.  
  32. ^ Wallberg AE, Pedersen K, Lendahl U, Roeder RG (November 2002). "p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro". Mol. Cell. Biol. 22 (22): 7812–9.  
  33. ^ Fryer CJ, Lamar E, Turbachova I, Kintner C, Jones KA (June 2002). "Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex". Genes Dev. 16 (11): 1397–411.  
  34. ^ a b Sartorelli V, Huang J, Hamamori Y, Kedes L (February 1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Mol. Cell. Biol. 17 (2): 1010–26.  
  35. ^ Youn HD, Grozinger CM, Liu JO (July 2000). "Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4". J. Biol. Chem. 275 (29): 22563–7.  
  36. ^ Youn HD, Liu JO (July 2000). "Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by controlling association of histone deacetylases and acetylases with MEF2". Immunity 13 (1): 85–94.  
  37. ^ Johnson LR, Johnson TK, Desler M, Luster TA, Nowling T, Lewis RE, Rizzino A (February 2002). "Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300". J. Biol. Chem. 277 (6): 4088–97.  
  38. ^ a b Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao ZX, Kumar S, Howley PM, Livingston DM (October 1998). "p300/MDM2 complexes participate in MDM2-mediated p53 degradation". Mol. Cell 2 (4): 405–15.  
  39. ^ a b Lau P, Bailey P, Dowhan DH, Muscat GE (January 1999). "Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD". Nucleic Acids Res. 27 (2): 411–20.  
  40. ^ a b De Luca A, Severino A, De Paolis P, Cottone G, De Luca L, De Falco M, Porcellini A, Volpe M, Condorelli G (February 2003). "p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor". Biochem. J. 369 (Pt 3): 477–84.  
  41. ^ Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7.  
  42. ^ García-Rodríguez C, Rao A (June 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". J. Exp. Med. 187 (12): 2031–6.  
  43. ^ Curtis AM, Seo SB, Westgate EJ, Rudic RD, Smyth EM, Chakravarti D, FitzGerald GA, McNamara P (February 2004). "Histone acetyltransferase-dependent chromatin remodeling and the vascular clock". J. Biol. Chem. 279 (8): 7091–7.  
  44. ^ Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K. "Recruitment of p300/CBP in p53-dependent signal pathways". Cell 1997 89(7):1175-84 [6]
  45. ^ An W, Kim J, Roeder RG (June 2004). "Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53". Cell 117 (6): 735–48.  
  46. ^ Pastorcic M, Das HK (November 2000). "Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene". J. Biol. Chem. 275 (45): 34938–45.  
  47. ^ Livengood JA, Scoggin KE, Van Orden K, McBryant SJ, Edayathumangalam RS, Laybourn PJ, Nyborg JK (March 2002). "p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300". J. Biol. Chem. 277 (11): 9054–61.  
  48. ^ Hasan S, Hassa PO, Imhof R, Hottiger MO (March 2001). "Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis". Nature 410 (6826): 387–91.  
  49. ^ Subramanian C, Hasan S, Rowe M, Hottiger M, Orre R, Robertson ES (May 2002). "Epstein-Barr virus nuclear antigen 3C and prothymosin alpha interact with the p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in regulation of transcription and histone acetylation". J. Virol. 76 (10): 4699–708.  
  50. ^ Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (December 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". J. Biol. Chem. 272 (52): 33435–43.  
  51. ^ Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. 274 (22): 15901–7.  
  52. ^ Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (October 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4.  
  53. ^ Kiernan R, Brès V, Ng RW, Coudart MP, El Messaoudi S, Sardet C, Jin DY, Emiliani S, Benkirane M (January 2003). "Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65". J. Biol. Chem. 278 (4): 2758–66.  
  54. ^ Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T (April 1997). "CREB-binding protein/p300 are transcriptional coactivators of p65". Proc. Natl. Acad. Sci. U.S.A. 94 (7): 2927–32.  
  55. ^ Pearson KL, Hunter T, Janknecht R (December 1999). "Activation of Smad1-mediated transcription by p300/CBP". Biochim. Biophys. Acta 1489 (2-3): 354–64.  
  56. ^ a b Nakashima K, Yanagisawa M, Arakawa H, Kimura N, Hisatsune T, Kawabata M, Miyazono K, Taga T (April 1999). "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300". Science 284 (5413): 479–82.  
  57. ^ Wotton D, Lo RS, Lee S, Massagué J (April 1999). "A Smad transcriptional corepressor". Cell 97 (1): 29–39.  
  58. ^ Pessah M, Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F, Gauthier JM, Atfi A (May 2001). "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6198–203.  
  59. ^ Grönroos E, Hellman U, Heldin CH, Ericsson J (September 2002). "Control of Smad7 stability by competition between acetylation and ubiquitination". Mol. Cell 10 (3): 483–93.  
  60. ^ Kim RH, Wang D, Tsang M, Martin J, Huff C, de Caestecker MP, Parks WT, Meng X, Lechleider RJ, Wang T, Roberts AB (July 2000). "A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction". Genes Dev. 14 (13): 1605–16.  
  61. ^ Eid JE, Kung AL, Scully R, Livingston DM (September 2000). "p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion". Cell 102 (6): 839–48.  
  62. ^ McDonald C, Reich NC (July 1999). "Cooperation of the transcriptional coactivators CBP and p300 with Stat6". J. Interferon Cytokine Res. 19 (7): 711–22.  
  63. ^ Huang S, Qiu Y, Stein RW, Brandt SJ (September 1999). "p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein". Oncogene 18 (35): 4958–67.  
  64. ^ Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (January 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". J. Biol. Chem. 278 (4): 2370–6.  
  65. ^ Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK (May 2002). "Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation". J. Biol. Chem. 277 (22): 20011–9.  
  66. ^ Gizard F, Lavallée B, DeWitte F, Hum DW (September 2001). "A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression". J. Biol. Chem. 276 (36): 33881–92.  
  67. ^ Sun Z, Pan J, Hope WX, Cohen SN, Balk SP (August 1999). "Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300". Cancer 86 (4): 689–96.  
  68. ^ Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (February 1999). "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell 96 (3): 405–13.  
  69. ^ Yao YL, Yang WM, Seto E (September 2001). "Regulation of transcription factor YY1 by acetylation and deacetylation". Mol. Cell. Biol. 21 (17): 5979–91.  
  70. ^ Lee JS, Galvin KM, See RH, Eckner R, Livingston D, Moran E, Shi Y (May 1995). "Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300". Genes Dev. 9 (10): 1188–98.  
  71. ^ Silverman ES, Du J, Williams AJ, Wadgaonkar R, Drazen JM, Collins T (November 1998). "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)". Biochem. J. 336 (1): 183–9.  

Further reading

  • Condorelli G, Giordano A (1998). "Synergistic role of E1A-binding proteins and tissue-specific transcription factors in differentiation". J. Cell. Biochem. 67 (4): 423–31.  
  • Marcello A, Zoppé M, Giacca M (2002). "Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator". IUBMB Life 51 (3): 175–81.  
  • Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205.  
  • 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.  
  • Le Rouzic E, Benichou S (2006). "The Vpr protein from HIV-1: distinct roles along the viral life cycle". Retrovirology 2: 11.  

External links

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