Anti-apoptotic role of the transcription factor NF-κb

The transcription factor NF-κB has moved to the forefront in the field of apoptosis, because of recent findings showing that activation of NF-κB prevents apoptosis of many different cell-types in a variety of cell culture and in vivo paradigms. Activation of NF-κB was first shown to mediate anti-apoptotic actions of tumor necrosis factor (TNF) in cultured neurons, and was subsequently shown to prevent death of cancer cells induced by chemotherapeutic agents. NF-κB is activated in response to engagement of several different cytokine and growth factor receptors, and in response to a variety of cell stressors. Oxidative stress and elevation of intracellular calcium levels are particularly important inducers of NF-κB activation. Activation of NF-κB can interupt apoptotic biochemical cascades at relatively early steps, prior to mitochondrial dysfunction and oxyradical production. Gene targets for NF-κB that may mediate its anti-apoptotic actions include the antioxidant enzyme Mn-superoxide dismutase and the calcium-binding protein calbindin D28k. The available data identify NF-κB as an important effector of "programmed cell life" a set of evolutionarily conserved biochemical and molecular cascades designed to prevent cell death in a variety of physiological and pathological settings. Because NF-κB may play roles in a range of diseases that involve abnormalities in regulation of cell death, pharmacological and genetic manipulations of NF-κB signaling are being developed in order to either enhance (e.g. cancer) or prevent (e.g. Alzheimer's disease) apoptosis.