The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

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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.