Epstein-Barr virus BHRF1 functions downstream of Bid cleavage and upstream of mitochondrial dysfunction to inhibit TRAIL-induced apoptosis in BJAB cells.
We have previously reported that TNF-related apoptosis inducing ligand (TRAIL) causes cleavage of Bid via activation of caspase-8 and the loss of mitochondrial membrane potential (DeltaPsim), resulting in apoptosis. Experiments with BJAB clones expressing Epstein-Barr virus (EBV) anti-apoptotic protein BHRF1 showed that BHRF1 drastically inhibited TRAIL-mediated apoptosis. Although Western blot analysis demonstrated that TRAIL-induced Bid cleavage was not inhibited by BHRF1, the decrease in DeltaPsim caused by TRAIL was effectively blocked by BHRF1. These findings suggest that in BJAB cells, BHRF1 acts downstream of Bid cleavage and upstream of mitochondrial damage, resulting in inhibition of TRAIL-induced apoptosis.
Kawanishi
Michiko
M
Department of Microbiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8315, Japan. kawanisi@mb.med.kyoto-u.ac.jp
Tada-Oikawa
Saeko
S
Kawanishi
Shosuke
S
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D017931:DNA Primers; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016393:Lymphoma, B-Cell; D008562:Membrane Glycoproteins / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C083278:BHRF1 protein, Human herpesvirus 4; C494814:BID protein, human; D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins