Natural 30 base pair and 69 base pair deletion variants of the LMP1 oncogene do stimulate NF-kappaB-mediated transcription

Oncogene
Sylvia RothenbergerH Knecht

Abstract

An increasing number of reports shows a link between the Epstein-Barr virus (EBV) and lymphoid neoplasia. The latent membrane protein 1 (LMP1) is likely to play a determinant role in this process since this EBV encoded protein has oncogenic properties and is usually expressed in EBV-associated lymphoproliferative diseases (LPD), except Burkitt's lymphoma. We previously identified in LPD patients mutational hot spots and a 30 bp or 69 bp deletion in the LMP1 gene region coding for the C-terminal domain. These deletions are located in an area shown to be important for the activation of the transcription factor NF-kappaB. These findings lead us to test whether these natural deletion variants may have a functional effect. We measured the stimulation of their activity using a luciferase reporter plasmid containing NF-kappaB responsive elements. We tested the NF-kappaB inducing activity of four naturally occurring LMP1 deletion variants. Our results show that these deletion variants activate NF-kappaB to the same level as the wild-type form, indicating that the crucial residues for NF-kappaB activation are conserved among the variants isolated and lie within the last 32 amino acids of the C-terminal domain of the LMP1 oncogene.

Citations

Feb 22, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shuyuan YouAnjia Han
Jul 1, 1997·Critical Reviews in Oncology/hematology·H KnechtP Brousset
Jun 1, 2000·Leukemia & Lymphoma·J Teruya-FeldsteinE S Jaffe
Jan 15, 2004·Pathology International·Hisashi HoriguchiHirotaka Ohse

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