Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-activated protein kinase (MAPK) signaling pathways (NF-κB/MAPK)

The NF-κB and MAPK signaling pathways are two fundamental intracellular cascades that regulate a wide array of cellular processes, including the immune response, inflammation, cell proliferation, and apoptosis (Oeckinghaus & Ghosh, 2009). NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) is a transcription factor complex that, when activated by stimuli like TNF-α or IL-1, translocates to the nucleus to drive the expression of pro-survival and pro-inflammatory genes (Hoesel & Schmid, 2013). The MAPK (Mitogen-activated protein kinase) pathways consist of three primary branches—ERK, JNK, and p38—which relay extracellular signals through a series of phosphorylation events to control cell growth and stress responses (Zhang & Liu, 2002). These pathways are frequently dysregulated in human diseases, particularly in cancer and chronic inflammatory conditions, where they contribute to uncontrolled cell growth and cytokine storms (Hoesel & Schmid, 2013). While they are often targeted by drugs such as MEK inhibitors (e.g., Trametinib) or proteasome inhibitors (e.g., Bortezomib), the complexity and crosstalk between these pathways present significant challenges for therapeutic intervention (Zhang & Liu, 2002). Effective modulation requires balancing the inhibition of pathological signaling with the preservation of essential physiological functions to minimize adverse effects like immunosuppression (Oeckinghaus & Ghosh, 2009).

Other names

NF-kappaB/MAPK axisNF-kB and MAPK pathwaysPro-inflammatory signaling cascades

Inhibition of kinase phosphorylation within the MAPK cascade (e.g., BRAF or MEK inhibitors) and inhibition of the IKK complex or proteasomal degradation of IκB to prevent NF-κB nuclear translocation (Oeckinghaus & Ghosh, 2009; Zhang & Liu, 2002).