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Perspectives
NF-κB and JNK: An Intricate Affair
Concetta Bubici, Salvatore Papa, Can G. Pham, Francesca Zazzeroni and Guido Franzoso
volume 3 | issue 12
december 2004Pages: 1524 - 1529
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NF-κB/Rel transcription factors block apoptosis or programmed cell death (PCD) induced by tumor necrosis factor (TNF)α. The antiapoptotic activity of NF-κB is also crucial for immunity, lymphocyte development, tumorigenesis, and cancer chemoresistance. With respect to TNF?, the NF-κB-mediated suppression of apoptosis involves inhibition of the c-Jun-N-terminal kinase (JNK) cascade. This inhibitory activity of NF-κB depends upon transcriptional upregulation of blockers of the JNK cascade such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase Gadd45β/Myd118. Moreover, NF-κB blunts accumulation of reactive oxygen species (ROS) induced by TNF?, and this antioxidant effect of NF-κB is also critical for inhibition of TNFα-induced JNK activation. Suppression of ROS by NF- κB is mediated by Ferritin heavy chain (FHC)—the primary iron-storage mechanism in cells—and possibly, by the mitochondrial enzyme Mn++ superoxide dismutase (Mn- SOD). Thus, induction of FHC and Mn-SOD represents an additional, indirect means by which NF-κB controls proapoptotic JNK signaling. These findings identify potential new targets for anti-inflammatory and anti-cancer therapy.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.