Nuclear factor kappa B and Activator protein 1-dependent transcription (NF-κB/AP-1 transcription)

NF-κB- and AP-1–dependent transcription refers to the gene expression programs regulated by two major families of transcription factors: Nuclear Factor kappa B (NF-κB) and Activator Protein 1 (AP-1) [1]. These factors are central mediators of the cellular response to stimuli such as cytokines, pathogens, and environmental stress [2]. NF-κB typically exists as a dimer (e.g., p50/p65) held inactive in the cytoplasm by IκB proteins, while AP-1 is a dimeric complex composed of proteins from the Jun and Fos families [3, 4]. Upon activation by upstream kinases like IKK and JNK, these factors translocate to the nucleus or increase their DNA-binding activity to drive the expression of pro-inflammatory and anti-apoptotic genes [5]. Dysregulation of this transcriptional activity is a hallmark of chronic inflammatory diseases and various cancers, where it promotes cell survival and proliferation [6]. Consequently, many therapeutic strategies aim to inhibit these pathways to treat autoimmune disorders and malignancies, though broad inhibition can lead to significant side effects like immunosuppression [7].

Other names

NF-kappaB and AP-1 signalingNF-kB/AP-1 pathwayPro-inflammatory transcriptionNF-kappaB/AP-1-mediated gene expression

Inhibition of nuclear translocation of transcription factors, inhibition of upstream kinases (IKK, JNK), or direct interference with DNA binding at promoter regions.