The transmembrane domains of the EBV-encoded latent membrane protein 1 (LMP1) variant CAO regulate enhanced signalling activity.

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Blake SM,Eliopoulos AG,Dawson CW,Young LS

doi

10.1006/viro.2001.0828

subject

Has Abstract

pub_date

2001-04-10 00:00:00

pages

278-87

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(01)90828-1

journal_volume

282

pub_type

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