Lack of cytotoxic property in a variant of Epstein-Barr virus latent membrane protein-1 isolated from nasopharyngeal carcinoma.
Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) is a membrane protein that activates multiple signaling pathways and transcription factors, including NF-kappaB. Our recent report demonstrated that expression of LMP1 induced programmed cell death in an NF-kappaB-dependent manner. In this study, we demonstrate that a variant CAO-LMP1 derived from EBV-infected nasopharyngeal carcinoma (NPC) does not induce cell death unlike the prototype B95.8-LMP1, although both types of LMP1 show NF-kappaB activation to a similar extent. Studies with chimeric or mutated proteins identified two amino acids in the transmembrane domain, which are commonly substituted in NPC-derived LMP1 variants, being critical for cell death induction by B95.8-LMP1. Furthermore, we show that the B95.8 transmembrane domain co-operates with NF-kappaB to trigger cell death program. Thus, our results reveal a particular feature of the transmembrane domain of tumor-derived CAO-LMP1 and suggest its possible contribution to the pathogenesis of NPC.
Nitta
Takeshi
T
Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Chiba
Ayako
A
Yamamoto
Naoki
N
Yamaoka
Shoji
S
D000595:Amino Acid Sequence; D000818:Animals; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D014644:Genetic Variation / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D017434:Protein Structure, Tertiary; D051381:Rats; D014162:Transfection; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D020169:Caspases