Induction of apoptosis by rewiring the signal transduction of Epstein-Barr virus oncoprotein LMP1 toward caspase activation.
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.
Hatzivassiliou
Eudoxia G
EG
Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, 34 Al. Fleming St., Vari 16672, Greece.
Tsichritzis
Theodore
T
Mosialos
George
G
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*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases