Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, Activator protein 1 signaling pathway (NF-κB signaling pathway, AP-1 signaling pathway)

The NF-κB/AP-1 signaling pathway refers to the combined or coordinated activity of two key transcription factor families—NF-κB and AP-1—that regulate gene expression in response to a variety of stimuli, including cytokines, pathogens, stress, and cellular damage. NF-κB is an inducible transcription factor complex consisting of five subunits (p65/RelA, RelB, c-Rel, p50, p52) sequestered in the cytoplasm by IκB proteins; upon activation, it translocates to the nucleus to induce genes governing immune responses, inflammation, cell survival, and apoptosis[1][3][4][5][6]. AP-1 is a dimeric transcription factor complex composed primarily of Jun, Fos, ATF, and MAF family proteins; it regulates gene expression for cell proliferation, differentiation, and stress responses. Both pathways are activated via overlapping but distinct upstream signals and can synergize, for example in reactivation of latent HIV, where both NF-κB and AP-1 binding sites are required at gene promoters[7]. Dysregulation of either or both pathways is implicated in diverse diseases ranging from cancer and autoimmune disorders to neurodegeneration and infectious diseases[1][2][3][4][5][7]. For structured use, "NF-κB signaling pathway" and "AP-1 signaling pathway" should typically be considered separate canonical targets; "NF-κB/AP-1 signaling pathway" is most accurately used as a descriptive term for their interactive effects in certain biological contexts, not as a molecular entity or fixed target.

Other names

Nuclear factor kappa B and Activator protein 1 pathwaysNF-κB and AP-1 pathwaysNF-kappaB/AP1 axis

Inhibition of IκB kinase (IKK) to block NF-κB activation Inhibition of upstream kinases (e.g., IRAK, TAK1) to suppress pathway signaling Blocking DNA binding of NF-κB or AP-1 to gene promoters Stabilization of IκB (NF-κB inhibitor) to retain NF-κB in cytoplasm Disruption of dimerization or nuclear translocation of transcription factors Inhibition of cytokine production downstream of transcription factor activation