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Papers In Press, published online ahead of print September 11, 2001
Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA 17033
Corresponding Author: sxs70{at}psu.edu
The Tax oncoprotein encoded by human T-cell leukemia virus induces both T-cell activation and apoptosis. The mechanism by which Tax induces apoptosis has remained unclear. Using genetically manipulated T-cell lines, we demonstrate that Tax-induced T-cell death is dependent on NF-kB signaling. Tax fails to induce apoptosis in T cells lacking IkB kinase gamma (IKKg), an essential component of the NF-kB signaling pathway. This defect was rescued when the mutant cells were reconstituted with exogenous IKKg. We further demonstrate that the Tax-induced T-cell death is mediated by TNF-related apoptosis-inducing ligand (TRAIL), since this event can be effectively inhibited by a TRAIL blocking antibody. Consistent with this functional aspect, Tax stimulates the expression of TRAIL mRNA. Finally, we provide genetic evidence demonstrating that the NF-kB signaling pathway is essential for TRAIL gene induction by both Tax and T-cell activation signals. These studies reveal a novel function of the NF-kB signaling pathway and suggest a key mechanism by which Tax induces T-cell death.
J. Biol. Chem, 10.1074/jbc.C100501200
Submitted on August 31, 2001
Revised on September 11, 2001
Accepted on September 11, 2001
NF-kB signaling pathway governs TRAIL gene expression and HTLV-I tax-induced T-cell death
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