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Journal of Virology, October 1998, p. 8105-8114, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Activation of the Epstein-Barr Virus Transcription Factor BZLF1
by 12-O-Tetradecanoylphorbol-13-Acetate-Induced
Phosphorylation
Matthias
Baumann,
Harald
Mischak,
Sascha
Dammeier,
Walter
Kolch,
Olivier
Gires,
Dagmar
Pich,
Reinhard
Zeidler,§
Henri-Jacques
Delecluse, and
Wolfgang
Hammerschmidt*
GSF-National Research Center for Environment
and Health, Institut für Klinische Molekularbiologie und
Tumorgenetik, Munich, Germany
Received 13 March 1998/Accepted 16 July 1998
BZLF1 is a member of the extended AP-1 family of transcription
factors which binds to specific BZLF1 sequence motifs within early Epstein-Barr virus (EBV) promoters and to closely related AP-1
motifs. BZLF1's activity is regulated at the transcriptional level as
well as through protein interactions and posttranslational modifications. Phorbol esters or immunoglobulin cross-linking both
reactivate EBV from latently infected B cells via transactivation of
BZLF1. We report here that the phorbol ester
12-O-tetradecanoylphorbol-13-acetate (TPA) is capable of
inducing BZLF1's activity even further. The induction occurs at the
posttranscriptional level and depends on a single serine
residue located in the DNA binding domain of BZLF1. This serine residue
(S186) is phosphorylated by protein kinase C in vitro and in vivo
after stimulation with TPA. Phosphorylation of S186 per se interferes
with the DNA binding affinity of BZLF1 in vitro but is mandatory for
TPA-induced increase in DNA binding of BZLF1, as shown in gel
retardation assays and reconstruction experiments with cellular
extracts. In transcriptional reporter assays, S186 is essential for
the activation of BZLF1 by TPA. Presumably, a yet-to-be-identified
cellular factor restores the DNA binding affinity and enhances the
transcriptional activity of S186-phosphorylated BZLF1, which is
required to induce the lytic phase of EBV's life cycle.
*
Corresponding author. Mailing address: GSF-National
Research Center for Environment and Health, Institut für
Klinische Molekularbiologie und Tumorgenetik,
Marchioninistrasse 25, D-81377 Munich, Germany. Phone: 49/89/7099-506.
Fax: 49/89/7099-500. E-mail: hammerschmidt{at}gsf.de.

Present address: Department of Nephrology, Franz-Volhard Klinikum
at the Max Delbrück Center, 13122 Berlin, Germany.

Present address: Beatson Institute for Cancer Research, Bearsden,
Glasgow G61 1BD, Scotland, United Kingdom.
§
Present address: Department of Otorhinolaryngology,
Ludwig-Maximilians-Universität, D-81377 Munich, Germany.
Journal of Virology, October 1998, p. 8105-8114, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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