Journal of Virology, January 2000, p. 83-90, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907
Received 20 May 1999/Accepted 7 September 1999
The hepatitis B virus X protein (pX) interacts directly with the
bZip transactivator CREB and the bZip repressors ICERII
and
ATF3, increasing their DNA-binding affinity in vitro and their transcriptional efficacy in vivo. However, the mechanism of
bZip-pX interaction and of the pX-mediated increase in the bZip
transcriptional efficacy remains to be understood. In this study with
deletion mutants of pX, we delineated a 67-amino-acid
region spanning residues 49 to 115 required for direct CREB, ATF3, and
ICER II
interaction in vitro and in vivo and increased bZip/CRE
binding in vitro. Transient transfections of the pX deletion mutants in
AML12 hepatocytes demonstrate that pX49-115 is as
effective as the full-length pX in enhancing the ATF3- and
ICERII
-mediated transrepression. However, this pX region
is inactive in increasing the transactivation efficacy of
CREB; additional amino acid residues present in pX49-140 are required to mediate the increased transactivation efficacy of
CREB in vivo. This requirement for different regions of pX in affecting
CREB transactivation suggests that amino acid residues 115 to
140 integrate additional events in effecting pX-mediated transactivation, such as concomitant interactions with select components of the basal transcriptional apparatus.
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