Death deflected: IL-15 inhibits TNF-α-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Rα chain

Silvia Bulfone-Paus, Elena Bulanova, Thomas Pohl, Vadim Budagian, Horst Dürkop, René Rückert, Ulrich Kunzendorf, Ralf Paus, Hans Krause

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)1575-1585
Number of pages11
JournalFASEB Journal
Volume13
Issue number12
StatePublished - Sep 8 1999
Externally publishedYes

Keywords

  • Cell death
  • IκB
  • L929
  • TNFR1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Bulfone-Paus, S., Bulanova, E., Pohl, T., Budagian, V., Dürkop, H., Rückert, R., Kunzendorf, U., Paus, R., & Krause, H. (1999). Death deflected: IL-15 inhibits TNF-α-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Rα chain. FASEB Journal, 13(12), 1575-1585.