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Originally published In Press as doi:10.1074/jbc.M111354200 on January 11, 2002
J. Biol. Chem., Vol. 277, Issue 12, 9982-9988, March 22, 2002
Hepatitis B Virus pX Interacts with HBXAP, a PHD
Finger Protein to Coactivate Transcription*
Meir
Shamay,
Orr
Barak ,
Gilad
Doitsh,
Israel
Ben-Dor, and
Yosef
Shaul§
From the Department of Molecular Genetics, Weizmann Institute of
Science, Rehovot 76100, Israel
Hepatitis B virus (HBV) gene expression is mainly
regulated at the transcription initiation level. The viral X protein
(pX) is a transcription coactivator/mediator targeting TFIIB for the recruitment of RNA polymerase II. Here we report a novel pX nuclear target designated HBXAP (hepatitis B virus X-associated protein). HBXAP
is a novel cellular nuclear protein containing a PHD (plant homology domain) finger, a domain shared by
many proteins that play roles in chromatin remodeling, transcription
coactivation, and oncogenesis. pX physically interacts with HBXAP
in vitro and in vivo via the HBXAP region
containing the PHD finger. At the functional level HBXAP increases HBV
transcription in a pX-dependent manner suggesting a role
for this interaction in the virus life cycle. Interestingly, HBXAP
collaborates with pX in coactivating the transcriptional activator
NF- B. Coactivation of NF- B was also observed in tumor necrosis
factor -treated cells suggesting that pX-HBXAP functional
collaboration localized downstream to the NF- B nuclear import.
Collectively our data suggest that pX recruits and potentiates a novel
putative transcription coactivator to regulate NF- B. The implication
of pX-HBXAP interaction in the development of hepatocellular carcinoma
is discussed.
*
This work was supported by the MINERVA Foundation, Germany.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(sreported in this paper for the HBXAP
mRNA has been deposited in the GenBankTM/EBI
Data Bank database with accession number(s) AAF61709.
The amino acid sequence of HBXAP reported in this paper can be accessed
through NCBI Protein Database under NCBI accession number
NP_057662.
Present address: University of Pennsylvania School of Medicine,
Philadelphia, PA 19104.
§
To whom correspondence should be addressed: Dept. of Molecular
Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Tel.:
972-8-9342320; Fax: 972-8-9344108; E-mail:
yosef.shaul@weizmann.ac.il.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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