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PMID: 12829857 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The zipper region of Epstein-Barr virus bZIP transcription factor Zta is necessary but not sufficient to direct DNA binding.

Journal of virology ·Vol. 77 ·No. 14 ·2003-07-00 ·Pages 8173-7

Hicks MR, Al-Mehairi SS, Sinclair AJ

Abstract

The viral bZIP transcription factor Zta (BZLF1, EB1, ZEBRA) mediates the switch between the latent and lytic cycles of Epstein-Barr virus (EBV). In part, its activity requires the formation of homodimers and interaction with specific DNA sequence elements (ZREs). Zta has an atypical zipper motif that has a lower stability than do typical bZIP proteins. Here we show that a synthetic peptide directed against the zipper can disrupt the DNA-binding function of Zta. This highlights the relevance of this region for the function of Zta and demonstrates that the zipper region is a potential target for therapeutic agents. We also unmask the relevance of a region adjacent to the zipper (CT region), which is required to direct the interaction of Zta with DNA and to transactivate ZRE-dependent promoters in vivo.

MeSH Terms
Amino Acid Sequence DNA/metabolism DNA-Binding Proteins/chemistry,genetics,metabolism Dimerization Gene Expression Regulation, Viral HeLa Cells Herpesvirus 4, Human/metabolism Humans Leucine Zippers Molecular Sequence Data Trans-Activators/chemistry,genetics,metabolism Transfection Viral Proteins
Chemicals
BZLF1 protein, Herpesvirus 4, Human DNA-Binding Proteins Trans-Activators Viral Proteins DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hicks Matthew R
School of Biological Sciences, University of Sussex, Brighton, East Sussex BN1 9QG, United Kingdom.
Al-Mehairi Salama S
Sinclair Alison J
References (36)
36 references, click to expand
  1. Biophysical analysis of natural variants of the multimerization region of Epstein-Barr virus lytic-switch protein BZLF1.
    J Virol. 2001 Jun;75(11):5381-4 PMID: 11333921
  2. Cell cycle analysis of Epstein-Barr virus-infected cells following treatment with lytic cycle-inducing agents.
    J Virol. 2001 May;75(10):4482-9 PMID: 11312318
  3. Investigating the tolerance of coiled-coil peptides to nonheptad sequence inserts.
    J Struct Biol. 2002 Jan-Feb;137(1-2):73-81 PMID: 12064935
  4. The Epstein-Barr virus immediate-early protein BZLF1 induces both a G(2) and a mitotic block.
    J Virol. 2002 Oct;76(19):10030-7 PMID: 12208981
  5. The Epstein-Barr virus immediate-early protein BZLF1 induces expression of E2F-1 and other proteins involved in cell cycle progression in primary keratinocytes and gastric carcinoma cells.
    J Virol. 2002 Dec;76(24):12543-52 PMID: 12438580
  6. CCAAT/enhancer binding protein alpha interacts with ZTA and mediates ZTA-induced p21(CIP-1) accumulation and G(1) cell cycle arrest during the Epstein-Barr virus lytic cycle.
    J Virol. 2003 Jan;77(2):1481-500 PMID: 12502863
  7. bZIP proteins of human gammaherpesviruses.
    J Gen Virol. 2003 Aug;84(Pt 8):1941-9 PMID: 12867624
  8. 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
  9. 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
  10. The Epstein-Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites.
    EMBO J. 1989 May;8(5):1447-53 PMID: 2548844
  11. The switch between EBV latency and replication.
    Yale J Biol Med. 1989 Mar-Apr;62(2):205-13 PMID: 2549738
  12. Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1.
    J Virol. 1990 Mar;64(3):1227-32 PMID: 2154606
  13. Structure and function of the Epstein-Barr virus BZLF1 protein.
    J Virol. 1990 May;64(5):2110-6 PMID: 2157874
  14. 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
  15. 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
  16. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.
    Nucleic Acids Res. 1990 Jun 25;18(12):3587-96 PMID: 2194165
  17. 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
  18. The BZLF1 protein of EBV has a coiled coil dimerisation domain without a heptad leucine repeat but with homology to the C/EBP leucine zipper.
    Oncogene. 1991 Feb;6(2):195-204 PMID: 1847997
  19. Predicting coiled coils from protein sequences.
    Science. 1991 May 24;252(5009):1162-4 PMID: 2031185
  20. Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia.
    J Virol. 1991 Jun;65(6):2868-74 PMID: 1851858
  21. 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
  22. Transcriptional synergy by the Epstein-Barr virus transactivator ZEBRA.
    J Virol. 1992 Aug;66(8):4803-13 PMID: 1321270
  23. Epstein-Barr virus transcription factors.
    Cell Growth Differ. 1992 Aug;3(8):557-63 PMID: 1327084
  24. The Epstein-Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin-dependent kinase inhibitors.
    EMBO J. 1996 Jun 3;15(11):2748-59 PMID: 8654372
  25. G0/G1 growth arrest mediated by a region encompassing the basic leucine zipper (bZIP) domain of the Epstein-Barr virus transactivator Zta.
    J Biol Chem. 1996 Dec 13;271(50):31799-802 PMID: 8943219
  26. Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene.
    Trends Microbiol. 1997 Oct;5(10):399-405 PMID: 9351176
  27. A general method to design dominant negatives to B-HLHZip proteins that abolish DNA binding.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12274-9 PMID: 9356439
  28. Sequence-based design of a peptide probe for the APC tumor suppressor protein.
    Curr Biol. 1998 Jul 2;8(14):823-30 PMID: 9663391
  29. The control of lytic replication of Epstein-Barr virus in B lymphocytes (Review).
    Int J Mol Med. 1998 Jan;1(1):137-42 PMID: 9852211
  30. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15613-7 PMID: 9861018
  31. Uncoiling c-Jun coiled coils: inhibitory effects of truncated Fos peptides on Jun dimerization and DNA binding in vitro.
    Biopolymers. 1998;47(4):277-83 PMID: 10036969
  32. Biology and disease associations of Epstein-Barr virus.
    Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29;356(1408):461-73 PMID: 11313005
  33. Dimerization of the Epstein-Barr virus ZEBRA protein in the yeast two-hybrid system. Comparison Of a ZEBRA variant with the B95-8 form.
    Biochimie. 2000 Feb;82(2):139-45 PMID: 10727769
  34. The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators.
    EMBO J. 2000 Jun 15;19(12):3080-9 PMID: 10856251
  35. Herpesvirus lytic replication and the cell cycle: arresting new developments.
    J Virol. 2001 May;75(10):4475-81 PMID: 11312317
  36. Role of c-myc regulation in Zta-mediated induction of the cyclin-dependent kinase inhibitors p21 and p27 and cell growth arrest.
    Virology. 2001 Jun 5;284(2):159-69 PMID: 11384216
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
2003-07-00
Pages
8173-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC161931
Subset
IM
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