Induction of cell death plays a crucial role in morphogenesis, homeostasis, immune tolerance and surveillance and chemotherapy. Supernumerary, damaged, transformed, or infected cells can be eliminated through intrinsic or extrinsic cell death programs. The induction of the extrinsic signal occurs when cytokines (i.e., CD95L, TRAIL, TNF-α) present in serum or anchored in immune cells (e.g., T-lymphocytes, natural killer cells) bind to their respective death receptors, namely CD95 (also called APO-1 or Fas), DR4 and DR5 or TNF-R1. Interaction with the ligand orchestrates aggregation and conformational alteration of the death receptors, whose intracellular domains recruit adaptor proteins (i.e., TRADD, FADD), which in turn drive, through protein/protein interactions, the induction of caspases evoking the death program.

Ministerio de Ciencia e Innovación of Spain (SAF2008-02251, and RD06/0020/1037 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986), and Junta de Castilla y León (CSI052A11-2, GR15-Experimental Therapeutics and Translational Oncology Program, and Biomedicine Project 2009).

Editorial [Hot topic: Stresses, Death Receptors and Plasma Membrane (Guest Editors: Patrick Legembre and Faustino Mollinedo)].

Peer reviewed