Raf-1 and protein kinase B regulate cell survival through the activation of NF-kappaB in hepatitis B virus X-expressing cells.
We previously demonstrated that activation of NF-kappaB 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-kappaB activation and their correlations with cell survival. XTT assays and colony generation assays revealed that inhibition of NF-kappaB 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 PKCalpha significantly diminished the HBx-mediated NF-kappaB 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-kappaB activation and also suppressed the cell survival. Our results suggest that the Raf-1 or PKB-mediated NF-kappaB activation promotes cell survival in HBx-expressing cells.
Um
Hae-Ryun
HR
Department of Biochemistry and Molecular Biology, Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu, Suwon, Republic of Korea.
Lim
Won-Chung
WC
Chae
Sun-Young
SY
Park
Sun
S
Park
Jeon Han
JH
Cho
Hyeseong
H
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology*; D011817:Rabbits; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins
D016328:NF-kappa B; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf