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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA112053-02
Application #
7073442
Study Section
Cancer Molecular Pathobiology Study Section (CAMP)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2005-06-15
Project End
2009-04-30
Budget Start
2006-06-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$368,361
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Fujii, Ryoji; Zhu, Changjun; Wen, Yunfei et al. (2006) HBXIP, cellular target of hepatitis B virus oncoprotein, is a regulator of centrosome dynamics and cytokinesis. Cancer Res 66:9099-107