XAP2, A NOVEL HEPATITIS-B VIRUS X-ASSOCIATED PROTEIN THAT INHIBITS X TRANSACTIVATION

The hepatitis B virus X protein is a promiscuous transcriptional trans activator, Transactivation by the X protein is most likely mediated th rough binding to different cellular factors, Using the yeast two-hybri d method, we have isolated a clone that encodes a novel X-associated c ellular protein XAP2. X and XAP2 interactions also occur in vitro. Ant iserum raised against XAP2 recognizes a cytoplasmic protein with an ap parent molecular mass of 36 kDa. The interaction between X and XAP2 re quires a small region on X containing amino acids 13-26. From Northern blot analyses, XAP2 is ubiquitously expressed in both liver-derived a nd non-liver-derived cell lines as well as in normal non-liver tissues , In contrast, XAP2 is expressed in very low level in the normal human liver, In transfection assays, overexpression of XAP2 abolishes trans activation by the X protein, Based on these results, we suggest that X AP2 is an important cellular negative regulator of the X protein, and that X-XAP2 interaction may play a role in HBV pathology.