XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation

The hepatitis B virus X protein is a promiscuous transcriptional transactivator, Transactivation by the X protein is most likely mediated through binding to different cellular factors, Using the yeast two-hybrid method, we have isolated a clone that encodes a novel X-associated cellular protein XAP2. X and XAP2 interactions also occur in vitro. Antiserum raised against XAP2 recognizes a cytoplasmic protein with an apparent molecular mass of 36 kDa. The interaction between X and XAP2 requires a small region on X containing amino acids 13-26. From Northern blot analyses, XAP2 is ubiquitously expressed in both liver-derived and 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 transactivation by the X protein, Based on these results, we suggest that XAP2 is an important cellular negative regulator of the X protein, and that X-XAP2 interaction may play a role in HBV pathology.