¹The Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL, USA

Correspondence: G Franzoso, Ben May Institute for Cancer Research, University of Chicago, 924 East 57th Street, BSLC, Room R420, Chicago, IL, 60637, USA. Tel: +1 773 834 0020; Fax: +1 773 702 4729; E-mail: gfranzos@midway.uchicago.edu

²Current address: Department of Experimental Medicine, The University of L'Aquila, Via Vetoio-Coppito 2, 67100 L'Aquila, Italy.

Received 2 November 2005; Revised 15 December 2005; Accepted 20 December 2005; Published online 3 February 2006.

Abstract

NF-B/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-B antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-B participates in a wide range of biological processes, including immunity, lymphopoiesis and development. It is also crucial for pathogenesis of various cancers, chronic inflammation and certain hereditary disorders. This participation of NF-B in survival signaling often involves an antagonism of PCD triggered by TNF-R-family receptors, and is mediated through a suppression of the formation of reactive oxygen species (ROS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of this antagonistic activity of NF-B on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-B promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.