The transmembrane domains of the EBV-encoded latent membrane protein 1 (LMP1) variant CAO regulate enhanced signalling activity.
Sequence variants of the Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) have been reported in association with EBV-linked malignancies but little is known about their effects on signalling pathways and phenotype. We have examined the ability of the nasopharyngeal carcinoma (NPC)-derived variant, CAO-LMP1 to activate the transcription factors NF-kappaB and AP-1 in epithelial cells. In this study, transient expression of CAO-LMP1 was found to activate higher levels of NF-kappaB and AP-1 than the prototype B95.8-LMP1 in human embryonic kidney (HEK) 293 cells and SV40-transformed keratinocytes (SVK). In addition, pulse-chase analysis revealed that CAO-LMP1 has a longer half-life than B95.8-LMP1. Chimera studies localised these phenomena to the transmembrane domains of CAO-LMP1, suggesting that this enhanced signalling capacity may be a consequence of its prolonged half-life. The ability of CAO-LMP1 to activate higher levels of NF-kappaB and AP-1 may contribute to its potent transforming properties.
Blake
S M
SM
CRC Institute for Cancer Studies, The University of Birmingham Medical School, Vincent Drive, Birmingham, Edgbaston, B15 2TT, United Kingdom.
Eliopoulos
A G
AG
Dawson
C W
CW
Young
L S
LS
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells; D014644:Genetic Variation / Q000235:genetics; D006207:Half-Life; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D006801:Humans; D015603:Keratinocytes; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000821:virology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014763:Viral Matrix Proteins; D004247:DNA