title: In the Crosshairs: NF-κB Targets the JNK Signaling Cascade.
abstract: NF-κB/Rel transcription factors are well-known for their roles in the regulation of inflammation and immunity. NF-κB also blocks programmed cell death (PCD) or apoptosis triggered by proinflammatory cytokine, tumor necrosis factor (TNF)α. Through transcriptional induction of distinct subsets of cyto-protective target genes, NF-κB inhibits the execution of apoptosis activated by this cytokine. This protective action is mediated, in part, by factors (such as A20, GADD45β, and XIAP) that downregulate the pro-apoptotic c-Jun-N-terminal (JNK) pathway. A suppression of reactive oxygen species (ROS), which are themselves major cell death-inducing elements activated by TNFα, is an additional protective function recently ascribed to NF-κB. This function of NF-κB involves an induction of mitochondrial anti-oxidant enzyme, manganese superoxide dismutase (Mn-SOD), and a control of cellular iron availability through upregulation of Ferritin heavy chain - one of two subunits of Ferritin, the major iron storage protein complex of the cell. An emerging view of NF-κB is that, while integrated, its actions in immunity and in promoting cell survival are executed through upregulation of distinct subsets of target genes. Thus, these inducible blockers of apoptosis may provide potential new targets to inhibit specific functions of NF-κB. In the future, this might allow for a better treatment of complex human diseases involving dysregulated NF-κB activity, including chronic inflammatory conditions and cancer.
authors.affiliation: The Ben May Institute for Cancer Research; The University of Chicago; 924 East 57th Street; Chicago, IL 60637, USA; U.S.A.
authors.forename: Can G
authors.initials: CG
authors.lastname: Pham
authors.forename: Salvatore
authors.initials: S
authors.lastname: Papa
authors.forename: Concetta
authors.initials: C
authors.lastname: Bubici
authors.forename: Francesca
authors.initials: F
authors.lastname: Zazzeroni
authors.forename: Guido
authors.initials: G
authors.lastname: Franzoso