Mechanisms of the HBX-interacting protein (HBXIP)

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DESCRIPTION (provided by applicant): Chronic Hepatitis B Virus (HBV) infection affects approximately 400 million people worldwide, and is associated with over one million deaths per year clue to hepatocellular carcinoma (HCC). The HBV genome contains only four open reading frames, encoding the C, S, and X proteins, and DNA polymerase. Among these, only the HBx protein has an association with cancer. The cellular targets of the HBx oncoprotein include the HBx-interacting protein (HBXIP). Recently, we demonstrated that HBXIP interacts with Survivin, a protein over-expressed in most human cancers that regulates both cell division and apoptosis. HBXIP collaborates with Survivin in suppressing apoptosis. Preliminary data also indicate that HBXIP localizes to mitotic structures in dividing cells, and like Survivin, it is required for mitosis and cell division. Based on these findings, we hypothesize that HBXIP is an important partner of Survivin and a dual regulator of cell division and apoptosis. We also hypothesize that the viral protein HBx targets HBXIP, thereby dysregulating the function of Survivin To test these hypotheses, we will: (1) determine the mechanisms by which HBXIP regulates cell division and apoptosis; and (2) explore the effects of HBx on HBXIP-Survivin interactions and functions associated with apoptosis and cell cycle regulation. Altogether, these investigations will define the role of HBXIP in regulating cell division and apoptosis, as well as providing new insights into the mechanisms of HBx in the pathogenesis of HCC.