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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
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Hepatitis B Virus pX Interacts with HBXAP, a PHD Finger Protein to Coactivate Transcription*

Meir Shamay, Orr BarakDagger , 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-kappa B. Coactivation of NF-kappa B was also observed in tumor necrosis factor alpha -treated cells suggesting that pX-HBXAP functional collaboration localized downstream to the NF-kappa B nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappa 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.

Dagger 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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