• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. May 1996; 70(5): 3068–3074.
PMCID: PMC190168

The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B, and 3C interact with RBPJ(kappa).

Abstract

The ability of Epstein-Barr virus (EBV) latent infection nuclear protein EBNA3C to activate transcription of two EBNA2-responsive genes and to inhibit EBNA2 activation of transcription in transient-transfection assays appears to be due to its ability to interact with RBPJkappa, a cell protein that links EBNA2 to its response elements. We now show that EBNA3A and EBNA3B expressed in non-EBV-infected Burkitt tumor lymphoblasts are similar to EBNA3C in binding to glutathione S-transferase-RBPJkappa in vitro and in coimmunoprecipitating from cell lysates with antibody to RBPJkappa. EBNA3A and EBNA3B can also inhibit the interaction of RBPJkappa with cognate DNA in vitro. Although EBNA3 open reading frames are each close to 1,000 codons long, EBNA3A amino acids 1 to 138, EBNA3B amino acids 1 to 311, and EBNA3C amino acids 1 to 183 are sufficient for RBPJkappa interaction, while EBNA3B amino acids I to 109 have less or no binding. The RBPJkappa interacting domains overlap with the most highly conserved domain (amino acids 90 to 320) among the EBNA3 proteins. Thus, the EBNA3 gene family appears to have evolved to differentially regulate promoters with RBPJkappa binding sites. EBNA2, EBNA3A, and EBNA3C are important in EBV transformation of primary human B lymphocytes. Their interaction with RBPJkappa links EBV transformation to the notch signaling pathway and the effects of activated notch in T-cell leukemogenesis.

Full Text

The Full Text of this article is available as a PDF (1.7M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Allday MJ, Farrell PJ. Epstein-Barr virus nuclear antigen EBNA3C/6 expression maintains the level of latent membrane protein 1 in G1-arrested cells. J Virol. 1994 Jun;68(6):3491–3498. [PMC free article] [PubMed]
  • Artavanis-Tsakonas S, Matsuno K, Fortini ME. Notch signaling. Science. 1995 Apr 14;268(5208):225–232. [PubMed]
  • Brou C, Logeat F, Lecourtois M, Vandekerckhove J, Kourilsky P, Schweisguth F, Israël A. Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless. Genes Dev. 1994 Oct 15;8(20):2491–2503. [PubMed]
  • Couso JP, Martinez Arias A. Notch is required for wingless signaling in the epidermis of Drosophila. Cell. 1994 Oct 21;79(2):259–272. [PubMed]
  • Dou S, Zeng X, Cortes P, Erdjument-Bromage H, Tempst P, Honjo T, Vales LD. The recombination signal sequence-binding protein RBP-2N functions as a transcriptional repressor. Mol Cell Biol. 1994 May;14(5):3310–3319. [PMC free article] [PubMed]
  • Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD, Sklar J. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991 Aug 23;66(4):649–661. [PubMed]
  • Fortini ME, Artavanis-Tsakonas S. The suppressor of hairless protein participates in notch receptor signaling. Cell. 1994 Oct 21;79(2):273–282. [PubMed]
  • Furukawa T, Maruyama S, Kawaichi M, Honjo T. The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development. Cell. 1992 Jun 26;69(7):1191–1197. [PubMed]
  • Henkel T, Ling PD, Hayward SD, Peterson MG. Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. Science. 1994 Jul 1;265(5168):92–95. [PubMed]
  • Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A. Signalling downstream of activated mammalian Notch. Nature. 1995 Sep 28;377(6547):355–358. [PubMed]
  • Johannsen E, Koh E, Mosialos G, Tong X, Kieff E, Grossman SR. Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1. J Virol. 1995 Jan;69(1):253–262. [PMC free article] [PubMed]
  • Kempkes B, Pich D, Zeidler R, Sugden B, Hammerschmidt W. Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA. J Virol. 1995 Jan;69(1):231–238. [PMC free article] [PubMed]
  • Khanna R, Burrows SR, Kurilla MG, Jacob CA, Misko IS, Sculley TB, Kieff E, Moss DJ. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med. 1992 Jul 1;176(1):169–176. [PMC free article] [PubMed]
  • Laux G, Adam B, Strobl LJ, Moreau-Gachelin F. The Spi-1/PU.1 and Spi-B ets family transcription factors and the recombination signal binding protein RBP-J kappa interact with an Epstein-Barr virus nuclear antigen 2 responsive cis-element. EMBO J. 1994 Dec 1;13(23):5624–5632. [PMC free article] [PubMed]
  • Lecourtois M, Schweisguth F. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling. Genes Dev. 1995 Nov 1;9(21):2598–2608. [PubMed]
  • Le Roux A, Kerdiles B, Walls D, Dedieu JF, Perricaudet M. The Epstein-Barr virus determined nuclear antigens EBNA-3A, -3B, and -3C repress EBNA-2-mediated transactivation of the viral terminal protein 1 gene promoter. Virology. 1994 Dec;205(2):596–602. [PubMed]
  • Ling PD, Rawlins DR, Hayward SD. The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a cellular enhancer-binding protein. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9237–9241. [PMC free article] [PubMed]
  • Marshall D, Sample C. Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator. J Virol. 1995 Jun;69(6):3624–3630. [PMC free article] [PubMed]
  • Matsunami N, Hamaguchi Y, Yamamoto Y, Kuze K, Kangawa K, Matsuo H, Kawaichi M, Honjo T. A protein binding to the J kappa recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif. Nature. 1989 Dec 21;342(6252):934–937. [PubMed]
  • Murray RJ, Kurilla MG, Brooks JM, Thomas WA, Rowe M, Kieff E, Rickinson AB. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med. 1992 Jul 1;176(1):157–168. [PMC free article] [PubMed]
  • Robertson ES, Grossman S, Johannsen E, Miller C, Lin J, Tomkinson B, Kieff E. Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa. J Virol. 1995 May;69(5):3108–3116. [PMC free article] [PubMed]
  • Sample J, Young L, Martin B, Chatman T, Kieff E, Rickinson A, Kieff E. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol. 1990 Sep;64(9):4084–4092. [PMC free article] [PubMed]
  • Schweisguth F, Posakony JW. Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates. Cell. 1992 Jun 26;69(7):1199–1212. [PubMed]
  • Silins SL, Sculley TB. Modulation of vimentin, the CD40 activation antigen and Burkitt's lymphoma antigen (CD77) by the Epstein-Barr virus nuclear antigen EBNA-4. Virology. 1994 Jul;202(1):16–24. [PubMed]
  • Tomkinson B, Kieff E. Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro. J Virol. 1992 May;66(5):2893–2903. [PMC free article] [PubMed]
  • Wang F, Gregory C, Sample C, Rowe M, Liebowitz D, Murray R, Rickinson A, Kieff E. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol. 1990 May;64(5):2309–2318. [PMC free article] [PubMed]
  • Yalamanchili R, Tong X, Grossman S, Johannsen E, Mosialos G, Kieff E. Genetic and biochemical evidence that EBNA 2 interaction with a 63-kDa cellular GTG-binding protein is essential for B lymphocyte growth transformation by EBV. Virology. 1994 Nov 1;204(2):634–641. [PubMed]
  • Zimber-Strobl U, Strobl LJ, Meitinger C, Hinrichs R, Sakai T, Furukawa T, Honjo T, Bornkamm GW. Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless. EMBO J. 1994 Oct 17;13(20):4973–4982. [PMC free article] [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    MedGen
    Related information in MedGen
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links
  • Taxonomy
    Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...