The FASEB Journal · 1999 · 152 citations · 36 references
Life SciencesCell BiologyImmunologyApoptosisCell SignalingSignal TransductionApoptosis RegulationApoptotic Signal TransductionApoptotic SignalingCell DeathCytokine BiologyDeath ReceptorsApoptosis Signaling PathwaysCell Death Signaling PathwaysCytokine-induced ApoptosisCytokine-mediated ApoptosisCytokine-mediated Cell DeathDeath DomainsTnfr1 SignalingTumor Necrosis Factor-mediated Apoptosis
Interleukin-15 (IL-15) is a potent inhibitor of several apoptosis pathways. One prominent path toward apoptosis is the ligand-induced association of TNF receptor 1 (TNFR1) with death domain adaptor proteins. Studying if and how IL-15 blocks TNFR1-mediated apoptosis in a murine fibroblast cell line (L929), we show here that IL-15 blocks TNFR1-induced apoptosis via IL-15Ralpha chain signaling. The intracellular tail of IL-15Ralpha shows sequence homologies to the TRAF2 binding motifs of CD30 and CD40. Most important, binding of IL-15 to IL-15Ralpha successfully competes with the TNFR1 complex for TRAF2 binding, which may impede assembly of key adaptor proteins to the TNFR1 complex, and induces IkappaBalpha phosphorylation. Thus, IL-15Ralpha chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-alpha and IL-15 surface as major opponents in apoptosis control.
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An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Amer A. Beg, David Baltimore · Science · 1996 · 3.1K citations
Suppression of TNF-α-Induced Apoptosis by NF-κB
Daniel J. Van Antwerp, Séamus J. Martin, Tal Kafri et al. · Science · 1996 · 2.6K citations