Nuclear factor kappa-light-chain-enhancer of activated B cells and Activator protein 1-regulated transcription (NF-κB/AP-1 transcription)

NF-κB and AP-1–regulated transcription refers to the coordinated gene expression programs controlled by the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Activator Protein 1 (AP-1) transcription factor complexes [1, 2]. These pathways are central mediators of the cellular response to inflammatory cytokines, growth factors, and environmental stress, often acting synergistically to regulate genes involved in the innate and adaptive immune responses, cell survival, and proliferation [3, 5]. NF-κB is typically a heterodimer of Rel family proteins (e.g., p65 and p50), while AP-1 is a dimeric complex composed of Jun and Fos proteins [2, 4]. Dysregulation of this transcriptional network is a hallmark of many chronic inflammatory diseases and various malignancies, where it promotes tumor growth, angiogenesis, and resistance to apoptosis [1, 4]. Because this entry describes a complex biological process involving multiple distinct protein complexes rather than a single molecular target, it is classified as a signaling pathway outcome [3, 5].

Other names

NF-κB/AP-1 signaling pathwayNF-kappaB and AP-1 mediated gene expressionPro-inflammatory transcription factor signalingNF-kB/AP-1 crosstalk

Drugs targeting this process typically act by inhibiting upstream activating kinases (such as the IKK complex for NF-κB or JNK/p38 MAPKs for AP-1), inhibiting the proteasome to prevent NF-κB activation, or by utilizing the glucocorticoid receptor to physically tether and antagonize these transcription factors, thereby preventing DNA binding and gene transactivation [1, 5].