FASEB J. 1999 Sep;13(12):1575-85.

Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain.External

Bulfone-Paus, S., Bulanova, E., Pohl, T., Budagian, V., Durkop, H., Ruckert, R., Kunzendorf, U., Paus, R., Krause, H.,
--- - Institute of Immunology, Department of Urology, Department of Pathology, University Hospital Benjamin Franklin, Free University, Berlin, Germany. bulfone@zedat.fu-berlin.de
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.
PMID: 10463949External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link TNFR1 Co-immunoprecipitation L929 10463949
DD TNFR1 Link TRADD Co-immunoprecipitation L929 10463949
(Link: click this icon to show interactions only between the two corresponding DDs)