Abstract
The activation of NF-κB inhibits apoptosis via a mechanism involving upregulation of various antiapoptotic genes, such as cellular FLICE-inhibitory protein (c-FLIP), Bcl-xL, A1/Bfl-1, and X chromosome-liked inhibitor of apoptosis (XIAP). In contrast, the activation of c-Jun N-terminal kinase (JNK) promotes apoptosis in a manner that is dependent on the cell type and the context of the stimulus. Recent studies have indicated that one of the antiapoptotic functions of NF-κB is to downregulate JNK activation. Further studies have also revealed that NF-κB inhibits JNK activation by suppressing accumulation of reactive oxygen species (ROS). In this review, we will focus on the signaling crosstalk between the NF-κB and JNK cascades via ROS.
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Abbreviations
- JNK:
-
c-Jun N-terminal kinase
- c-FLIP:
-
cellular FLICE-inhibitory protein
- XIAP:
-
X chromosome-linked inhibitor of apoptosis
- ROS:
-
reactive oxygen species
- TNF:
-
tumor necrosis factor
- IL-1:
-
interleukin-1
- IκB:
-
inhibitor of κB
- IKK:
-
IκB kinase
- MAPK:
-
mitogen-activated protein kinase
- ERK:
-
extracellular signal-regulated kinase
- ASK1:
-
apoptosis-signal regulating kinase 1
- MEKK:
-
MAP/ERK kinase kinase
- TAK1:
-
TGFβ-activated kinase 1
- MEFs:
-
murine embryonic fibroblasts
- TRAF:
-
TNF rceptor-associated factor
- c-IAP:
-
cellular inhibitor of apoptosis
- ES:
-
embrynonic stem
- GADD:
-
growth arrest and DNA damage-inducing protein
- SOD:
-
superoxide dismutase
- GPx:
-
glutathione peroxidase
- PRx:
-
peroxiredoxin
- NOX:
-
NADPH oxidase
- BHA:
-
butylated hydroxylanisole
- NAC:
-
N-acetyl cystein
- MKP:
-
MAP kinase phosphatase
- MnSOD:
-
manganese-dependent SOD
- FHC:
-
ferritin heavy chain
- mPT:
-
membrane permeability transition
- AIF:
-
apoptosis-inducing factor
- HSP:
-
heat shock protein
- CHX:
-
cycloheximide
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Acknowledgements
We thank CF Ware and S Shimizu for critically reading the manuscript. We also thank D Wallach for the comments on the manuscript. KO and HN are supported in part by a Grant-in-Aid for 21st Century COE Research and Scientific Research (B) from Japan Society for the Promotion of Science (JSPS), Japan. HN is supported by Takeda Science Foundation and by a Grant from Human Frontier Science Program (HFSP).
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Nakano, H., Nakajima, A., Sakon-Komazawa, S. et al. Reactive oxygen species mediate crosstalk between NF-κB and JNK. Cell Death Differ 13, 730–737 (2006). https://doi.org/10.1038/sj.cdd.4401830
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DOI: https://doi.org/10.1038/sj.cdd.4401830
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