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Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance

Oncogene volume 25, pages 6731–6748 (2006)Cite this article

Abstract

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-κB), 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-κB exerts on ROS and JNK activities. This NF-κB-imposed restraint on ROS and JNK signaling is crucial for antagonism of PCD elicited by the proinflammatory cytokine tumor necrosis factor (TNF)α and likely other triggers. Effectors of this antagonistic cross-talk between NF-κB and ROS/JNK pathways have recently been identified. Because of the key roles that the prosurvival function of NF-κB plays in organismal physiology and disease, gaining a further mechanistic understanding of this cross-talk and NF-κB-dependent survival may be key to developing new therapies for the treatment of widespread human illnesses, such as cancer and chronic inflammatory conditions.

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Acknowledgements

This research was supported in part by NIH Grants R01-CA84040 and R01-CA098583.

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    C Bubici, S Papa, K Dean & G Franzoso

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Bubici, C., Papa, S., Dean, K. et al. Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene 25, 6731–6748 (2006). https://doi.org/10.1038/sj.onc.1209936

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