title: The amino-terminus and membrane-spanning domains of LMP-1 inhibit cell proliferation.
abstract: The LMP-1 oncoprotein of EBV is required to maintain proliferation of infected B-cells and shares several features with CD40, TNF-R1, and related receptors. Members of this family can bind TRAF and TRADD molecules and activate NF-kappaB and AP-1, as can LMP-1. While CD40 and TNF-R1 are dependent on binding their ligands for their signaling, LMP-1 apparently is not. We have found that LMP-1 can act as a governor of cell proliferation and thereby limit its own activities. Its inhibition of proliferation is not mediated by apoptosis but results in cytostasis in four cell lines tested. The structural moiety of LMP-1 that distinguishes it from CD40 and TNF-R1, its amino-terminus and multiple membrane spanning segments, alone can mediate its cytostatic activity.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, WI 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kaykas
authors.forename: B
authors.initials: B
authors.lastname: Sugden
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D006131:Growth Inhibitors / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D010449:Peptide Mapping; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006131:Growth Inhibitors; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D014763:Viral Matrix Proteins