title: Induction of apoptosis by rewiring the signal transduction of Epstein-Barr virus oncoprotein LMP1 toward caspase activation.
abstract: The Epstein-Barr virus latent membrane protein 1 (LMP1) is an oncoprotein which mimics activated tumor necrosis factor receptor family members. Here we demonstrate the principle that an inducible association of the LMP1 cytoplasmic carboxyl terminus with caspase-8 by a heterodimerizing agent causes apoptosis. This process depends on the catalytic activity of caspase-8 and the ability of LMP1 to oligomerize constitutively at the plasma membrane. Our data indicate that chemical inducers of the association of the LMP1 carboxyl terminus with caspase-8 can kill LMP1-expressing cells selectively. Such compounds could be used as chemotherapeutic agents for LMP1-associated malignancies.
authors.affiliation: Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, 34 Al. Fleming St., Vari 16672, Greece.
authors.forename: Eudoxia G
authors.initials: EG
authors.lastname: Hatzivassiliou
authors.forename: Theodore
authors.initials: T
authors.lastname: Tsichritzis
authors.forename: George
authors.initials: G
authors.lastname: Mosialos
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007668:Kidney; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases