¹Unité de Signalisation Moléculaire et Activation Cellulaire (SMAC), URA 2582 Centre National de la Recherche Scientifique (CNRS), Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France

Correspondence: A Israël, A Israël, Unité de Signalisation Moléculaire et Activation Cellulaire (SMAC), URA 2582 Centre National de la Recherche Scientifique (CNRS), Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France. Tel: +33 1 40 61 30 37; Fax: +33 1 40 61 30 40; E-mail: aisrael@pasteur.fr

Received 7 November 2005; Accepted 2 December 2005; Published online 27 January 2006.

Abstract

A major regulator of lymphocyte survival and activation is the transcription factor nuclear factor-B (NF-B). Controlled activation of NF-B is essential for the immune and inflammatory response as well as for cell proliferation and protection against apoptosis. The NEMO/IB kinase (IKK) complex is the central integrator of most stimuli leading to NF-B activation, but a detailed knowledge of the upstream events is available only for a limited number of stimuli. In particular, although most players have probably been identified, relatively little is known about the detailed molecular mechanisms involved in the cascade leading to NF-B activation following engagement of the T-cell receptor by a foreign antigen. In this review, we discuss recent insights into this specific signal transduction cascade, and the way it is controlled both spatially and temporally.