Natural 30 base pair and 69 base pair deletion variants of the LMP1 oncogene do stimulate NF-kappaB-mediated transcription.
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.
Rothenberger
S
S
Institut de Pharmacologie et Toxicologie, Université de Lausanne, Switzerland.
Bachmann
E
E
Berger
C
C
McQuain
C
C
Odermatt
B F
BF
Knecht
H
H
D001482:Base Composition; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D005814:Genes, Viral / Q000235:genetics*; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism*; D009857:Oncogenes / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000502:physiology; D015678:Viral Structural Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins; D008156:Luciferases