NF-kappaB is required for cell death induction by latent membrane protein 1 of Epstein-Barr virus.
NF-kappaB is a transcription factor known to promote or antagonize cell death depending on cell types and stimuli. Here, we demonstrate that expression of latent membrane protein 1 (LMP1), an Epstein-Barr virus (EBV)-encoded membrane protein, triggers programmed cell death in an NF-kappaB-dependent manner. Co-expression of NF-kappaB inhibitors completely prevented activation of NF-kappaB and LMP1-induced cell death. Addition therein of RelA, an active subunit of NF-kappaB, restored the NF-kappaB activation and cell death induction by LMP1, but RelA alone did not induce cell death. These results indicate that the activation of NF-kappaB is required for cell death induced by LMP1. Moreover, LMP1 induced activation of caspase-3 via the activation of NF-kappaB. Studies with z-VAD-fmk, a caspase inhibitor, indicated that NF-kappaB mediated both caspase-dependent and -independent death pathways. In conclusion, the cell death induced by LMP1 uncovered caspase-dependent and -independent death pathways both of which require NF-kappaB.
Nitta
Takeshi
T
Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Chiba
Ayako
A
Yamashita
Atsuya
A
Rowe
Martin
M
Israël
Alain
A
Reth
Michael
M
Yamamoto
Naoki
N
Yamaoka
Shoji
S
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004789:Enzyme Activation; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids; D051381:Rats; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases