Home LiteratureArticle Details
PMID: 8234266 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Serine-173 of the Epstein-Barr virus ZEBRA protein is required for DNA binding and is a target for casein kinase II phosphorylation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 21 ·1993-11-01 ·Pages 10115-9

Kolman JL, Taylor N, Marshak DR, Miller G

Abstract

An Epstein-Barr virus-encoded protein, ZEBRA, mediates the switch from latency to the viral lytic life cycle. ZEBRA's domain structure and DNA binding specificity resemble that of cellular transcriptional activators such as c-Fos/c-Jun. We show that ZEBRA, like c-Jun, is phosphorylated by casein kinase II (CKII). The principal site of phosphorylation is serine-173 (S173), five amino acids upstream of the basic DNA recognition domain. CKII phosphorylation abrogated ZEBRA's capacity to bind its target DNA sequences. S173 is a functional component of ZEBRA's DNA binding domain, since mutation of S173 to alanine (S173A) reduced DNA binding in vitro to 10% of wild-type levels. Transcriptional activation of a native viral promoter in vivo by mutant S173A was also reduced markedly. Reversible phosphorylation of S173 is likely to be an important means of regulating ZEBRA's activity in vivo.

MeSH Terms
Alanine Amino Acid Sequence B-Lymphocytes/metabolism Base Sequence Binding Sites Casein Kinase II Cloning, Molecular DNA Primers DNA-Binding Proteins/metabolism Escherichia coli Herpesvirus 4, Human/metabolism Humans Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Point Mutation Polymerase Chain Reaction Promoter Regions, Genetic Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins c-fos/metabolism Proto-Oncogene Proteins c-jun/metabolism Recombinant Fusion Proteins/metabolism Serine Trans-Activators/metabolism Transcription, Genetic Transcriptional Activation Viral Proteins/metabolism
Chemicals
BZLF1 protein, Herpesvirus 4, Human DNA Primers DNA-Binding Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Recombinant Fusion Proteins Trans-Activators Viral Proteins Serine Casein Kinase II Protein Serine-Threonine Kinases Alanine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kolman J L
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510.
Taylor N
Marshak D R
Miller G
References (43)
43 references, click to expand
  1. Viral proteins associated with the Epstein-Barr virus transactivator, ZEBRA.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):378-82 PMID: 1309613
  2. Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity.
    Science. 1991 Dec 20;254(5039):1814-6 PMID: 1684878
  3. Myc and Max associate in vivo.
    Genes Dev. 1992 Jan;6(1):71-80 PMID: 1730411
  4. Fos is phosphorylated by p34cdc2, cAMP-dependent protein kinase and protein kinase C at multiple sites clustered within regulatory regions.
    Oncogene. 1991 Dec;6(12):2179-85 PMID: 1766667
  5. Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers.
    Genes Dev. 1992 Feb;6(2):166-76 PMID: 1737614
  6. Phosphorylation of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA.
    Virology. 1992 Jun;188(2):916-20 PMID: 1316687
  7. Transcriptional synergy by the Epstein-Barr virus transactivator ZEBRA.
    J Virol. 1992 Aug;66(8):4803-13 PMID: 1321270
  8. The regulation of transcription by phosphorylation.
    Cell. 1992 Aug 7;70(3):375-87 PMID: 1643656
  9. Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity.
    Cell. 1992 Sep 4;70(5):777-89 PMID: 1516134
  10. Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts.
    Mol Cell Biol. 1992 Oct;12(10):4694-705 PMID: 1328860
  11. Changing Epstein-Barr viral ZEBRA protein into a more powerful activator enhances its capacity to disrupt latency.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4436-40 PMID: 8389449
  12. 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
  13. 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
  14. Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides.
    J Biol Chem. 1987 Jul 5;262(19):9136-40 PMID: 3474230
  15. Protein serine/threonine kinases.
    Annu Rev Biochem. 1987;56:567-613 PMID: 2956925
  16. Activation of casein kinase II in response to insulin and to epidermal growth factor.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):8834-8 PMID: 3321056
  17. A new Epstein-Barr virus transactivator, R, induces expression of a cytoplasmic early antigen.
    J Virol. 1988 Jul;62(7):2274-84 PMID: 2836611
  18. 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
  19. Expression of the BZLF1 latency-disrupting gene differs in standard and defective Epstein-Barr viruses.
    J Virol. 1989 Apr;63(4):1721-8 PMID: 2538652
  20. Serum-stimulated cell growth causes oscillations in casein kinase II activity.
    J Biol Chem. 1989 May 5;264(13):7345-8 PMID: 2708368
  21. Regulating cell growth: casein-kinase-II-dependent phosphorylation of nuclear oncoproteins.
    Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:91-5 PMID: 3076091
  22. The Epstein-Barr virus immediate-early gene product, BMLF1, acts in trans by a posttranscriptional mechanism which is reporter gene dependent.
    J Virol. 1989 Sep;63(9):3870-7 PMID: 2548002
  23. Scissors-grip model for DNA recognition by a family of leucine zipper proteins.
    Science. 1989 Nov 17;246(4932):911-6 PMID: 2683088
  24. Protein phosphatases come of age.
    J Biol Chem. 1989 Dec 25;264(36):21435-8 PMID: 2557326
  25. The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions.
    J Virol. 1990 Mar;64(3):1143-55 PMID: 2154599
  26. Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1.
    J Virol. 1990 Mar;64(3):1227-32 PMID: 2154606
  27. Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation.
    Nature. 1990 Apr 5;344(6266):517-22 PMID: 2157164
  28. Structure and function of the Epstein-Barr virus BZLF1 protein.
    J Virol. 1990 May;64(5):2110-6 PMID: 2157874
  29. 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
  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. Casein kinase II enhances the DNA binding activity of serum response factor.
    Genes Dev. 1990 Jun;4(6):955-67 PMID: 2200737
  32. Casein kinase 2: an 'eminence grise' in cellular regulation?
    Biochim Biophys Acta. 1990 Sep 24;1054(3):267-84 PMID: 2207178
  33. 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
  34. Negative regulation of the BZLF1 promoter of Epstein-Barr virus.
    J Virol. 1991 Jul;65(7):3647-55 PMID: 1645787
  35. Mutation of serum response factor phosphorylation sites and the mechanism by which its DNA-binding activity is increased by casein kinase II.
    Mol Cell Biol. 1991 Jul;11(7):3652-9 PMID: 2046671
  36. 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
  37. Signal transduction and gene control.
    Curr Opin Cell Biol. 1991 Jun;3(3):467-73 PMID: 1832548
  38. Phosphorylation of transcriptional factors and cell-cycle-dependent proteins by casein kinase II.
    Curr Opin Cell Biol. 1991 Jun;3(3):474-83 PMID: 1654061
  39. Efficient transcription of the Epstein-Barr virus immediate-early BZLF1 and BRLF1 genes requires protein synthesis.
    J Virol. 1991 Dec;65(12):7073-7 PMID: 1658397
  40. Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation.
    Virology. 1991 Dec;185(2):922-8 PMID: 1660209
  41. 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
  42. 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
  43. Myc oncoproteins are phosphorylated by casein kinase II.
    EMBO J. 1989 Apr;8(4):1111-9 PMID: 2663470
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
DOI
10.1073/pnas.90.21.10115
Published
1993-11-01
Pages
10115-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47724
Subset
IM
Grants
NCI NIH HHS · CA12055 · United States
NCI NIH HHS · CA16038 · United States
NCI NIH HHS · CA52228 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.21.10115 PMC Full Text View journal details
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]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2