Induction of apoptosis by rewiring the signal transduction of Epstein-Barr virus oncoprotein LMP1 toward caspase activation |
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Authors: | Hatzivassiliou Eudoxia G Tsichritzis Theodore Mosialos George |
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Institution: | Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, 34 Al. Fleming St., Vari 16672, Greece. |
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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. |
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