Raf-1 and protein kinase B regulate cell survival through the activation of NF-κB in hepatitis B virus X-expressing cells

We previously demonstrated that activation of NF-κB by the hepatitis B virus X (HBx) gene plays an important role in cell survival. In the present study, we explored the upstream mediators of NF-κB activation and their correlations with cell survival. XTT assays and colony generation assays revealed that inhibition of NF-κB activation indeed increased cell death in HBx-expressing cells. Utilizing inactivating mutants of signal transducers, we showed that dominant negative mutants of stress-activated protein kinase/extracellular signal-regulated kinase (SEK1) or PKCα significantly diminished the HBx-mediated NF-κB activation. However, neither of these mutants significantly affected the cell survival in colony generation assays. In contrast, inactivating mutants of Raf-1 or PKB (protein kinase B)/Akt abrogated the HBx-mediated NF-κB activation and also suppressed the cell survival. Our results suggest that the Raf-1 or PKB-mediated NF-κB activation promotes cell survival in HBx-expressing cells.