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Death deflected: IL‐15 inhibits TNF‐α‐mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL‐15Rα chain
Author(s) -
Silvia Bulfone–Paus∥,
Elena Bulanova,
Thomas Pohl,
Vadim Budagian,
Horst Dürkop,
René Rückert,
Ulrich Kunzendorf,
Ralf Paus,
Hans Krause
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.12.1575
Subject(s) - traf2 , signal transducing adaptor protein , microbiology and biotechnology , apoptosis , tumor necrosis factor alpha , programmed cell death , signal transduction , death domain , phosphorylation , biology , chemistry , immunology , biochemistry , tumor necrosis factor receptor
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.