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PMID: 8617212 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells.

The EMBO journal ·Vol. 15 ·No. 2 ·1996-01-15 ·Pages 375-82

Jochner N, Eick D, Zimber-Strobl U, Pawlita M, Bornkamm GW, Kempkes B

Abstract

A conditional mutant of Epstein-Barr virus nuclear antigen 2 (EBNA2) regulated by estrogen was employed to study the effect of EBNA2 on the cellular phenotype. Activation of EBNA2 in lymphoblastoid cell lines (LCLs) and in B cell lymphoma lines resulted in down-regulation of cell surface IgM and Ig-mu steady-state RNA expression. In LCLs, activation of EBNA2 is required for maintaining proliferation, whereas in Burkitt's lymphoma (BL) cell lines with t(8;14) translocations, activation of EBNA2 induces growth arrest. In these cells, Northern and nuclear run-on analyses revealed rapid simultaneous repression of Ig-mu and c-myc transcription as early as 30 min after activation of EBNA2. Since c-myc expression is under the control of the Ig heavy chain locus in BL cell lines with a t(8;14) translocation, we propose that Ig-mu and c-myc are down-regulated by EBNA2 through a common mechanism.

MeSH Terms
Antigens, Viral/metabolism Blotting, Northern Burkitt Lymphoma/genetics Cell Division Cell Nucleus/metabolism Chromosomes, Human, Pair 14 Chromosomes, Human, Pair 8 DNA-Binding Proteins/metabolism Epstein-Barr Virus Nuclear Antigens Gene Expression Regulation, Neoplastic Genes, myc Humans Immunoglobulin M/biosynthesis Immunoglobulin mu-Chains/biosynthesis Kinetics Proto-Oncogene Proteins c-myc/biosynthesis Receptors, Antigen, B-Cell/biosynthesis Recombinant Fusion Proteins/metabolism Repressor Proteins/metabolism Time Factors Transcription, Genetic Transfection Translocation, Genetic Tumor Cells, Cultured
Chemicals
Antigens, Viral DNA-Binding Proteins Epstein-Barr Virus Nuclear Antigens Immunoglobulin M Immunoglobulin mu-Chains Proto-Oncogene Proteins c-myc Receptors, Antigen, B-Cell Recombinant Fusion Proteins Repressor Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jochner N
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum fur Umwelt und Gesundheit, München, Germany.
Eick D
Zimber-Strobl U
Pawlita M
Bornkamm G W
Kempkes B
References (55)
55 references, click to expand
  1. Epstein-Barr virus: adaptation to a life within the immune system.
    Trends Microbiol. 1994 Apr;2(4):125-30 PMID: 8012755
  2. Epstein-Barr virus strategy in normal and neoplastic B cells.
    Cell. 1994 Jun 17;77(6):791-3 PMID: 8004668
  3. The Epstein-Barr virus nuclear antigen 2 transactivator is directed to response elements by the J kappa recombination signal binding protein.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7568-72 PMID: 8052621
  4. Identification and characterization of an Epstein-Barr virus nuclear antigen 2-responsive cis element in the bidirectional promoter region of latent membrane protein and terminal protein 2 genes.
    J Virol. 1994 Nov;68(11):6947-58 PMID: 7933076
  5. Crucial sequences within the Epstein-Barr virus TP1 promoter for EBNA2-mediated transactivation and interaction of EBNA2 with its responsive element.
    J Virol. 1994 Nov;68(11):7497-506 PMID: 7933133
  6. 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):4973-82 PMID: 7957063
  7. 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 PMID: 7975264
  8. Differential Epstein-Barr virus gene expression in B-cell subsets recovered from lymphomas in SCID mice after transplantation of human peripheral blood lymphocytes.
    J Virol. 1995 Jan;69(1):150-5 PMID: 7983705
  9. 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):253-62 PMID: 7983717
  10. 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):5624-32 PMID: 7988559
  11. The human J kappa recombination signal sequence binding protein (RBP-J kappa) targets the Epstein-Barr virus EBNA2 protein to its DNA responsive elements.
    EMBO J. 1994 Dec 1;13(23):5633-8 PMID: 7988560
  12. Pharmacologic activation of expression of immunodominant viral antigens: a new strategy for the treatment of Epstein-Barr-virus-associated malignancies.
    Curr Top Microbiol Immunol. 1995;194:145-54 PMID: 7534666
  13. 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):3108-16 PMID: 7707539
  14. Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator.
    J Virol. 1995 Jun;69(6):3624-30 PMID: 7745710
  15. Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas.
    Proc Natl Acad Sci U S A. 1974 Aug;71(8):3283-6 PMID: 4369887
  16. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments.
    Cell. 1980 Nov;22(1 Pt 1):197-207 PMID: 6775818
  17. Immunoglobulin secretion by cell lines derived from African and American undifferentiated lymphomas of Burkitt's and non-Burkitt's type.
    J Immunol. 1982 Sep;129(3):1336-42 PMID: 6286763
  18. Deletion of the nontransforming Epstein-Barr virus strain P3HR-1 causes fusion of the large internal repeat to the DSL region.
    J Virol. 1982 Sep;43(3):952-68 PMID: 6292473
  19. Extreme instability of myc mRNA in normal and transformed human cells.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046-50 PMID: 6594679
  20. The use of lymphomatous and lymphoblastoid cell lines in the study of Burkitt's lymphoma.
    IARC Sci Publ. 1985;(60):309-18 PMID: 3934070
  21. Aberrant c-myc RNAs of Burkitt's lymphoma cells have longer half-lives.
    EMBO J. 1985 Dec 30;4(13B):3717-25 PMID: 3004968
  22. Geographical prevalence of two types of Epstein-Barr virus.
    Virology. 1986 Oct 15;154(1):56-66 PMID: 3019008
  23. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells.
    EMBO J. 1986 Oct;5(10):2599-607 PMID: 3023050
  24. Identification of the 37-kDa protein displaying a variable interaction with the erythroid cell membrane as glyceraldehyde-3-phosphate dehydrogenase.
    J Biol Chem. 1987 Jan 15;262(2):649-53 PMID: 3027061
  25. Immunofluorescence and herpes-type virus particles in the P3HR-1 Burkitt lymphoma cell line.
    J Virol. 1967 Oct;1(5):1045-51 PMID: 4912237
  26. EBV-transformed lymphoblastoid cell lines down-regulate EBNA in parallel with secretory differentiation.
    Int J Cancer. 1987 Mar 15;39(3):404-8 PMID: 3546163
  27. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3452-6 PMID: 3033649
  28. Epstein-Barr virus (EBV) induces expression of B-cell activation markers on in vitro infection of EBV-negative B-lymphoma cells.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):8060-4 PMID: 2825176
  29. Epstein-Barr virus gene expression in nasopharyngeal carcinoma.
    J Gen Virol. 1988 May;69 ( Pt 5):1051-65 PMID: 2836550
  30. Immunoglobulin mRNA stability varies during B lymphocyte differentiation.
    EMBO J. 1988 Apr;7(4):1041-6 PMID: 3136013
  31. A movable and regulable inactivation function within the steroid binding domain of the glucocorticoid receptor.
    Cell. 1988 Sep 23;54(7):1073-80 PMID: 2843290
  32. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma.
    Int J Cancer. 1988 Sep 15;42(3):329-38 PMID: 2843473
  33. Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells.
    Nature. 1989 Jul 6;340(6228):66-8 PMID: 2662015
  34. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes.
    Nature. 1989 Aug 3;340(6232):393-7 PMID: 2547164
  35. Expression of normal and translocated c-myc alleles in Burkitt's lymphoma cells: evidence for different regulation.
    EMBO J. 1989 Jul;8(7):1965-72 PMID: 2551669
  36. A protein binding to the J kappa recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif.
    Nature. 1989 Dec 21-28;342(6252):934-7 PMID: 2556644
  37. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558-62 PMID: 2556717
  38. Stable transfection of Epstein-Barr virus (EBV) nuclear antigen 2 in lymphoma cells containing the EBV P3HR1 genome induces expression of B-cell activation molecules CD21 and CD23.
    J Virol. 1990 Mar;64(3):1002-13 PMID: 2154588
  39. cis-acting regulatory elements near the Epstein-Barr virus latent-infection membrane protein transcriptional start site.
    J Virol. 1990 Apr;64(4):1855-8 PMID: 2157069
  40. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein.
    J Virol. 1990 May;64(5):2126-34 PMID: 2157875
  41. The level of c-fgr RNA is increased by EBNA-2, an Epstein-Barr virus gene required for B-cell immortalization.
    J Virol. 1990 Jun;64(6):2530-6 PMID: 2159528
  42. Epstein-Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7390-4 PMID: 2170976
  43. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene.
    J Virol. 1991 Jan;65(1):415-23 PMID: 1845900
  44. EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus.
    J Virol. 1991 May;65(5):2164-9 PMID: 1850003
  45. Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3942-6 PMID: 1850841
  46. Control of c-myc regulation in normal and neoplastic cells.
    Adv Cancer Res. 1991;56:1-48 PMID: 2028839
  47. Identification of critical cis elements involved in mediating Epstein-Barr virus nuclear antigen 2-dependent activity of an enhancer located upstream of the viral BamHI C promoter.
    J Virol. 1992 May;66(5):2846-52 PMID: 1313905
  48. myc function and regulation.
    Annu Rev Biochem. 1992;61:809-60 PMID: 1497324
  49. Epstein-Barr virus (EBV) nuclear-antigen-2-induced up-regulation of CD21 and CD23 molecules is dependent on a permissive cellular context.
    Int J Cancer. 1993 Jan 2;53(1):153-60 PMID: 8416201
  50. The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter.
    EMBO J. 1993 Jan;12(1):167-75 PMID: 8381349
  51. Expression of Epstein-Barr virus latent gene products and related cellular activation and adhesion molecules in Hodgkin's disease and non-Hodgkin's lymphomas arising in patients without overt pre-existing immunodeficiency.
    Hum Pathol. 1993 Jul;24(7):725-9 PMID: 8100553
  52. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation.
    Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150-4 PMID: 8415670
  53. 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):9237-41 PMID: 8415684
  54. Ongoing mutations in the N-terminal domain of c-Myc affect transactivation in Burkitt's lymphoma cell lines.
    Oncogene. 1994 Mar;9(3):759-63 PMID: 8108117
  55. Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa.
    Science. 1994 Jul 1;265(5168):92-5 PMID: 8016657
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-01-15
Pages
375-82
Language
English
Region
England
NLM ID
8208664
PMCID
PMC449952
Subset
IM
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