Home LiteratureArticle Details
PMID: 8389449 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Changing Epstein-Barr viral ZEBRA protein into a more powerful activator enhances its capacity to disrupt latency.

Baumann R, Grogan E, Ptashne M, Miller G

Abstract

The Epstein-Barr viral transcriptional activator ZEBRA induces expression of viral early lytic genes when introduced into cells bearing latent Epstein-Barr virus. We show here that a ZEBRA-herpes simplex viral protein 16 (VP16) fusion protein induces early viral lytic gene expression in Epstein-Barr virus-containing cells more efficiently than does wild-type ZEBRA. The fusion protein is also a more powerful transcriptional activator in these cells, as assayed with reporter constructs. Our experiments also suggest that ZEBRA manifests a function required for full activity on certain natural promoters but not on promoters bearing oligomerized ZEBRA binding sites; this function cannot be provided by VP16.

MeSH Terms
Cells, Cultured DNA-Binding Proteins/metabolism,physiology Gene Expression Regulation, Viral Herpesvirus 4, Human/pathogenicity Humans In Vitro Techniques Protein Binding RNA, Messenger/genetics Recombinant Fusion Proteins/genetics Structure-Activity Relationship Trans-Activators/physiology Transcription Factors/genetics,metabolism Transcriptional Activation Viral Proteins Virus Replication
Chemicals
BZLF1 protein, Herpesvirus 4, Human DNA-Binding Proteins RNA, Messenger Recombinant Fusion Proteins Trans-Activators Transcription Factors Viral Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Baumann R
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510.
Grogan E
Ptashne M
Miller G
References (38)
38 references, click to expand
  1. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  2. Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors.
    Cell. 1992 Sep 18;70(6):1007-19 PMID: 1326406
  3. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription.
    J Mol Biol. 1984 Nov 25;180(1):1-19 PMID: 6096556
  4. Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4085-9 PMID: 2987963
  5. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes.
    Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870-4 PMID: 2994050
  6. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter.
    EMBO J. 1986 Dec 1;5(12):3243-9 PMID: 3028777
  7. Interferon-beta gene regulation: tandemly repeated sequences of a synthetic 6 bp oligomer function as a virus-inducible enhancer.
    Cell. 1987 May 8;49(3):357-67 PMID: 3032451
  8. Identification of an Epstein-Barr virus early gene encoding a second component of the restricted early antigen complex.
    Virology. 1987 Sep;160(1):151-61 PMID: 2820125
  9. Binding of the virion protein mediating alpha gene induction in herpes simplex virus 1-infected cells to its cis site requires cellular proteins.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7061-5 PMID: 2823252
  10. A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence.
    Cell. 1988 Feb 12;52(3):425-34 PMID: 2830986
  11. Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation.
    Cell. 1988 Feb 12;52(3):435-45 PMID: 2830987
  12. The SV40 enhancer contains two distinct levels of organization.
    Nature. 1988 May 5;333(6168):40-5 PMID: 2834649
  13. Transfer and expression of plasmids containing human cytomegalovirus immediate-early gene 1 promoter-enhancer sequences in eukaryotic and prokaryotic cells.
    Biotechnol Appl Biochem. 1988 Feb;10(1):6-12 PMID: 2841949
  14. A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins.
    Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347-51 PMID: 2842768
  15. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression.
    Genes Dev. 1988 Jun;2(6):718-29 PMID: 2843425
  16. GAL4-VP16 is an unusually potent transcriptional activator.
    Nature. 1988 Oct 6;335(6190):563-4 PMID: 3047590
  17. How eukaryotic transcriptional activators work.
    Nature. 1988 Oct 20;335(6192):683-9 PMID: 3050531
  18. The Epstein-Barr virus (EBV) early promoter DR contains a cis-acting element responsive to the EBV transactivator EB1 and an enhancer with constitutive and inducible activities.
    J Virol. 1989 Feb;63(2):607-14 PMID: 2536096
  19. The Epstein-Barr virus (EBV) BZLF1 immediate-early gene product differentially affects latent versus productive EBV promoters.
    J Virol. 1989 Apr;63(4):1729-36 PMID: 2538653
  20. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos.
    EMBO J. 1989 Jan;8(1):127-32 PMID: 2540954
  21. Responsiveness of the Epstein-Barr virus NotI repeat promoter to the Z transactivator is mediated in a cell-type-specific manner by two independent signal regions.
    J Virol. 1989 Jul;63(7):3040-50 PMID: 2542612
  22. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle.
    J Virol. 1989 Jul;63(7):3109-16 PMID: 2542618
  23. The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators.
    J Virol. 1989 Sep;63(9):3878-83 PMID: 2548003
  24. Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1.
    J Virol. 1990 Mar;64(3):1217-26 PMID: 2154605
  25. Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1.
    J Virol. 1990 Mar;64(3):1227-32 PMID: 2154606
  26. The switch between latency and replication of Epstein-Barr virus.
    J Infect Dis. 1990 May;161(5):833-44 PMID: 2157769
  27. Structure and function of the Epstein-Barr virus BZLF1 protein.
    J Virol. 1990 May;64(5):2110-6 PMID: 2157874
  28. In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein.
    J Virol. 1990 Jun;64(6):2560-8 PMID: 2159531
  29. The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif.
    J Virol. 1990 Jul;64(7):3358-69 PMID: 2161945
  30. The Epstein-Barr virus (EBV) BMRF1 promoter for early antigen (EA-D) is regulated by the EBV transactivators, BRLF1 and BZLF1, in a cell-specific manner.
    J Virol. 1990 Aug;64(8):3753-9 PMID: 2164595
  31. Synergism between distinct enhanson domains in viral induction of the human beta interferon gene.
    Mol Cell Biol. 1990 Aug;10(8):3987-93 PMID: 2370859
  32. Evidence for coiled-coil dimer formation by an Epstein-Barr virus transactivator that lacks a heptad repeat of leucine residues.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9459-63 PMID: 2174563
  33. Transcriptional interference between the EBV transcription factors EB1 and R: both DNA-binding and activation domains of EB1 are required.
    Nucleic Acids Res. 1991 Mar 25;19(6):1251-8 PMID: 1851554
  34. ZEBRA and a Fos-GCN4 chimeric protein differ in their DNA-binding specificities for sites in the Epstein-Barr virus BZLF1 promoter.
    J Virol. 1991 Aug;65(8):4033-41 PMID: 1649314
  35. Characterization of the Epstein-Barr virus BZLF1 protein transactivation domain.
    J Virol. 1992 Feb;66(2):922-9 PMID: 1309920
  36. An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected].
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2150-4 PMID: 1532252
  37. Transcriptional synergy by the Epstein-Barr virus transactivator ZEBRA.
    J Virol. 1992 Aug;66(8):4803-13 PMID: 1321270
  38. High efficiency polyoma DNA transfection of chloroquine treated cells.
    Nucleic Acids Res. 1983 Mar 11;11(5):1295-308 PMID: 6298741
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1993-05-15
Pages
4436-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46526
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]