Association of the Epstein-Barr virus latent membrane protein 1 with lipid rafts is mediated through its N-terminal region.
The latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus acts like a constitutively activated receptor of the tumor necrosis factor receptor (TNFR) family and is enriched in lipid rafts. We showed that LMP1 is targeted to lipid rafts in transfected HEK 293 cells, and that the endogenous TNFR-associated factor 3 binds LMP1 and is recruited to lipid rafts upon LMP1 expression. An LMP1 mutant lacking the C-terminal 55 amino acids (Cdelta55) behaves like the wild-type (WT) LMP1 with respect to membrane localization. In contrast, a mutant with a deletion of the 25 N-terminal residues (Ndelta25) does not concentrate in lipid rafts but still binds TRAF3, demonstrating that cell localization of LMP1 was not crucial for TRAF3 localization. Moreover, Ndelta25 inhibited WT LMP1-mediated induction of the transcription factors NF-kappaB and AP-1. Morphological data indicate that Ndelta25 hampers WT LMP1 plasma membrane localization, thus blocking LMP1 function.
Rothenberger
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Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland. Sylvia.RothenbergerAubert@ib.unil.ch
Rousseaux
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Knecht
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Bender
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Legler
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Bron
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D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D012995:Solubility; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D016328:NF-kappa B; D011506:Proteins; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D018808:Transcription Factor AP-1; D014763:Viral Matrix Proteins