The Epstein-Barr virus oncoprotein LMP1 inhibits the activity of viral or cellular promoters without inducing cytostasis.
The Latent Membrane Protein 1 of the Epstein-Barr virus is required for human B lymphocyte immortalization and functions as a constitutively activated member of the TNF-receptor family, through recruitment of TRAFs and TRADD molecules on its Carboxy-terminal domain, leading to the activation of NF-kappaB and AP1 transcription factors. The formation of the signaling complexes requires LMP1 oligomerization, a role assigned to the membrane-spanning domains of the molecule. There is, however, increasing evidence that these membrane-spanning domains are not only confined to oligomerization but play a direct role in downregulation of promoter activity and cytostasis. Here, we describe a new inhibitory activity which is effective on viral or cellular promoters (even the endogenous ones), requires only membrane-spanning domains 3-4 or 5-6 and is neither associated with cytostasis nor with apoptosis.
Centre de Physiopathologie Toulouse Purpan, U563 INSERM, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France.
Stéphane
S
Narbonnet
Bernard
B
Mariamé
D000956:Antigens, Viral / Q000502:physiology; D001483:Base Sequence; D002051:Burkitt Lymphoma; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D005091:Exons; D017930:Genes, Reporter; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
D000956:Antigens, Viral; D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014157:Transcription Factors; D014763:Viral Matrix Proteins