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J Virol, August 1998, p. 6291-6297, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Herpesvirus Transactivator VP16 Mimics a Human
Basic Domain Leucine Zipper Protein, Luman, in Its Interaction
with HCF
Rui
Lu,1,2
Ping
Yang,1
Sharmila
Padmakumar,1 and
Vikram
Misra1,*
Department of Veterinary Microbiology,
Western College of Veterinary Medicine, University of Saskatchewan,
Saskatoon, Saskatchewan S7N 5B4,1 and
Saskatchewan Health Services Utilization and Research
Commission, Saskatoon, Saskatchewan S7N OW8,2
Canada
Received 13 March 1998/Accepted 28 April 1998
In human cells infected with herpes simplex virus (HSV), viral gene
expression is initiated by the virion protein VP16. VP16 does not bind
DNA directly but forms a multiprotein complex on the viral
immediate-early gene promoters with two cellular proteins: the POU
domain protein Oct-1 and host cell factor (HCF; also called C1, VCAF,
and CFF). Despite its apparent role in stabilizing the VP16-induced
transcription complex, the natural biological role of HCF is unclear.
Only recently HCF has been implicated in control of the cell cycle. To
determine the role of HCF in cells and answer why HSV has evolved an
HCF-dependent mechanism for the initiation of the lytic cycle, we
identified the first human ligand for HCF (R. Lu et al., Mol. Cell.
Biol. 17:5117-5126, 1997). This protein, Luman, is a
member of the CREB/ATF family of transcription factors that
can activate transcription from promoters containing
cyclic AMP response elements (CRE). Here we provide evidence that
Luman and VP16 share two important structural features: an acidic
activation domain and a common mechanism for binding
HCF. We found that Luman, its homolog in Drosophila,
dCREB-A (also known as BBF-2), and VP16 bind to HCF by a motif,
(D/E)HXY(S/A), present in all three proteins. In addition, a mutation
(P134S) in HCF that prevents VP16 binding also abolishes its
binding to Luman and dCREB-A. We also show that while interaction with
HCF is not required for the ability of Luman to activate transcription
when tethered to the GAL4 promoter, it appears to be essential for
Luman to activate transcription through CRE sites. These data suggest
that the HCF-Luman interaction may represent a conserved mechanism for
transcriptional regulation in metazoans, and HSV mimics this
interaction with HCF to monitor the physiological state of the host
cell.
*
Corresponding author. Mailing address: Department of
Veterinary Microbiology, Western College of Veterinary Medicine,
University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N
5B4, Canada. Phone: (306) 966-7218. Fax: (306) 966-7244. E-mail:
misra{at}duke.usask.ca.
J Virol, August 1998, p. 6291-6297, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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