Tumor necrosis factor (TNF) and phorbol ester induce TNF-related apoptosis-inducing ligand (TRAIL) under critical involvement of NF-kappa B essential modulator (NEMO)/IKKgamma.
We show that tumor necrosis factor (TNF) and phorbol 12-myristate 13-acetate (PMA) induce TNF-related apoptosis-inducing ligand (TRAIL) in T cells. In cells deficient for NF-kappaB essential modulator (NEMO)/IKKgamma, an essential component of the NF-kappaB-inducing I-kappaB kinase (IKK) complex, induction of TRAIL expression was completely abrogated but was recovered in cells restored for IKKgamma expression. In cells deficient for receptor-interacting protein expression TNF, but not PMA-induced TRAIL expression was blocked. Inhibition of protein synthesis with cycloheximide blocked PMA, but not TNF-induced up-regulation of TRAIL. As both TNF and PMA rapidly induce NF-kappaB activation this suggests that NEMO/IKKgamma-dependent activation of the NF-kappaB pathway is necessary but not sufficient for up-regulation of TRAIL in T cells. The capability of the NF-kappaB pathway to induce the potent death ligand TRAIL may explain the reported proapoptotic features of this typically antiapoptotic pathway.
Siegmund
D
D
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Hausser
A
A
Peters
N
N
Scheurich
P
P
Wajant
H
H
D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D051550:I-kappa B Kinase; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D013755:Tetradecanoylphorbol Acetate