Journal article

NF-kappa B inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2

Philip Diessenbacher, Mike Hupe, Martin R Sprick, Andreas Kerstan, Peter Geserick, Tobias L Haas, Tina Wachter, Manfred Neumann, Henning Walczak, John Silke, Martin Leverkus

JOURNAL OF INVESTIGATIVE DERMATOLOGY | NATURE PUBLISHING GROUP | Published : 2008

Abstract

Death ligands not only activate a death program but also regulate inflammatory signalling pathways, for example, through NF-kappaB induction. Although tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TNF both activate NF-kappaB in human keratinocytes, only TRAIL potently induces apoptosis. However, when induction of NF-kappaB was inhibited with a kinase dead IKK2 mutant (IKK2-KD), TNF- but not TRAIL-induced apoptosis was dramatically enhanced. Acquired susceptibility to TNF-induced apoptosis was due to increased caspase-8 activation. To investigate the mechanism of resistance of HaCaT keratinocytes to TNF-induced apoptosis, we analyzed a panel of NF-kappaB-regulated ..

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University of Melbourne Researchers