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-15Rα chain signaling. The intracellular tail of IL-15Rα shows sequence homologies to the TRAF2 binding motifs of CD30 and CD40. Most important, binding of IL-15 to IL-15Rα successfully competes with the TNFR1 complex for TRAF2 binding, which may impede assembly of key adaptor proteins to the TNFR1 complex, and induces IκBα phosphorylation. Thus, IL-15Rα chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-α and IL-15 surface as major opponents in apoptosis control.
|Original language||English (US)|
|Number of pages||11|
|State||Published - Sep 8 1999|
- Cell death
ASJC Scopus subject areas
- Molecular Biology