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

Abstract

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.

Epstein–Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen

“…Sequencing the insert showed that clone 436 was identical with a previously identi®ed cellular gene that encodes Xap-2, a protein that associates with Hepatitis B virus X antigen (Kuzhandaivelu et al, 1996).…”

“…The p38 subunit is identical with Xap-2, a cellular protein that also binds the N-terminus of Hepatitis B virus X antigen (Meyer et al, 1998). Cotransfection of Xap-2 with X antigen inhibits the X mediated transcriptional transactivation in CAT assays (Kuzhandaivelu et al, 1996).…”

The Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression

“…XAP2 is a 37 kDa phosphorylated protein 170 that was first identified through its ability to interact with the hepatitis B virus X protein. 171 Crosslinking studies performed by Perdew in 1992 showed that, in addition to two molecules of HSP90, the AhR tetrameric complex contains a ~ 46 kDa protein. 172 Five years later, three separate laboratories identified that the murine, human, and simian-forms of XAP2 (also known as AIP or ARA9) are components of the latent AhR complex.…”

Phosphodiesterases link the aryl hydrocarbon receptor complex to cyclic nucleotide signaling

“…Another component of the AHR complex is XAP2 (also known as ARA9 or AIP), a 38-kDa protein that was initially identified as a protein binding to the hepatitis B virus X protein [41] and in parallel also as binding partner of AHR [42][43][44]. XAP2 shares sequence identity with FKBP52, an immunophilin of the family of FK506 binding proteins and an established component of the glucocorticoid receptor complex.…”

“…Association of XAP2 with transcription factors appears to be a rather general phenomenon. XAP2 interacts with hepatitis B virus protein X [41], EBNA-3 (Epstein-Barr-virus encoded nuclear antigen 3) [53] and thyroid hormone receptor [54] besides other molecules, like survivin, an anti-apoptotic molecule that has been implicated not only in preservation of cell viability but also in essential regulatory circuitries of cell division [55]. These versatile roles of XAP2 are reflected in the observation that deletion of the XAP2 gene in mice causes embryonic lethality associated with gross defects in the development of the cardiovascular system [56].…”