Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance.
Reactive oxygen species (ROS) are emerging as key effectors in signal transduction. This role of ROS is especially evident in the pathways leading to programmed cell death (PCD) elicited in response to certain stress stimuli and cytokines. In these pathways, cytotoxic ROS signaling appears to be mediated in part by activation of the c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) cascade. Another pathway that is under ROS-mediated control in some systems is that leading to activation of transcription factor nuclear factor-kappa B (NF-kappaB), which is a central regulator of immunity, inflammation and cell survival. Remarkably, new evidence has unveiled the existence of a reciprocal, negative control that NF-kappaB exerts on ROS and JNK activities. This NF-kappaB-imposed restraint on ROS and JNK signaling is crucial for antagonism of PCD elicited by the proinflammatory cytokine tumor necrosis factor (TNF)alpha and likely other triggers. Effectors of this antagonistic cross-talk between NF-kappaB and ROS/JNK pathways have recently been identified. Because of the key roles that the prosurvival function of NF-kappaB plays in organismal physiology and disease, gaining a further mechanistic understanding of this cross-talk and NF-kappaB-dependent survival may be key to developing new therapies for the treatment of widespread human illnesses, such as cancer and chronic inflammatory conditions.
Bubici
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C
The Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Papa
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S
Dean
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K
Franzoso
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G
D000818:Animals; D017209:Apoptosis; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D048670:MAP Kinase Kinase 4