Chimeric and Mutated Variants of LMP1: A Helpful Tool to Analyze the Structure-Function Relationship of a Pseudoreceptor
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Epstein Barr virus (EBV) efficiently immortalizes human B cells in vitro generating lymphoblastoid cell lines (LCL) with indefinite lifespan. Latent membrane protein 1 (LMP1) belongs to a set of nine viral proteins expressed in vitro, five of which appear to be essential for B-cell immortalization (for review,
see
ref.
1
). LMP1 is a membrane protein composed of a short cytoplasmic aminoterminus (24 residues), a transmembrane domain with six membrane-spanning segments separated by short reverse turns and a long cytoplasmic carboxy terminus (200 residues;
see
Fig. 1 ) (
2
–
4
). Genetic analysis has shown that LMP1 is indispensable but not sufficient for B-cell immortalization (
5
–
7
). In the last years the hypothesis was raised that LMP1 might act as a constitutively active receptor because it integrates into the plasma membrane and patches as an oligomer (
3
,
8
). This idea was further supported by LMP1’s ability to bind molecules involved in the signaling cascade of the TNF-receptor family members (
9
–
12
). In analogy to known receptors such as CD40 or TNF-R2, LMP1 activates cellular transcription factors of the NFкB and AP-1 family (
13
–
15
). Transcriptional activation of target genes is supposed to play a key role in EBV-mediated immortalization as well as LMP1-mediated oncogenicity.
Fig. 1.
Schematic representation of the wild-type LMP1 molecule. LMP1wt consists of a short amino terminus (24 AA), six transmembrane segments separated by short reverse turns and a long carboxy terminus (200 AA). Recognition site for the S12 αLMP1 antibody within the LMP1 molecule is annotated (αLMP1).
