TY - JOUR
T1 - NF-κB is required for cell death induction by latent membrane protein 1 of Epstein-Barr virus
AU - Nitta, T
AU - Chiba, A
AU - Yamashita, A
AU - Rowe, Martin
AU - Israel, A
AU - Reth, M
AU - Yamamoto, N
AU - Yamaoka, S
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037400185&partnerID=8YFLogxK
U2 - 10.1016/S0898-6568(02)00141-9
DO - 10.1016/S0898-6568(02)00141-9
M3 - Article
C2 - 12618217
VL - 15
SP - 423
EP - 433
JO - Cellular Signalling
JF - Cellular Signalling
ER -