Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma

Figure 1 Proposed model to explain the link between hepatitis B virus X protein, p38/MAPK, SATB1, hepatoma upregulated protein, and survivin in mediating anti-apoptotic effects during cisplatin treatment. HBx upregulates the anti-apoptotic protein survivin through induction of p38/MAPK and ERK/MAPK pathways. Another less defined ERK/MAPK pathway which may regulate survivin independently of HURP is also shown. HBx: Hepatitis B virus X protein; HURP: Hepatoma upregulated protein.

Figure 2 Simplified model illustrating the oncogenic properties of hepatitis B virus X protein and hepatoma upregulated protein in human liver cancer. In this cycle of gankyrin/MDM2-enhanced p53 degradation, HURP reduces MDM2-mediated ubiquitination of gankyrin, leading to accumulation of gankyrin in both normal and tumorigenic cells. Downstream effects of HURP appear to include malignant cell transformation and prevention of apoptosis induced by chemotherapeutic drug, processes which may in turn lead to the development of a chemoresistant cellular phenotype. HBx: Hepatitis B virus X protein; HURP: Hepatoma upregulated protein.