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

The MAPK/NF-κB signaling pathway components encompass a broad array of intracellular signaling molecules, including kinases such as RAF, MEK, and IKK, and transcription factors like p65 and p50, which integrate extracellular signals to regulate gene expression [1]. These pathways are critical for mediating cellular responses to growth factors, cytokines, and environmental stress, playing pivotal roles in cell survival, proliferation, and the innate immune response [2]. In many cancers and inflammatory disorders, these components are dysregulated or mutated, leading to persistent signaling that promotes tumor growth, metastasis, and chronic inflammation [3]. Pharmacological intervention often targets specific nodes within these pathways, such as the use of MEK inhibitors like trametinib or proteasome inhibitors like bortezomib to disrupt the cascade and induce apoptosis in malignant cells [4]. However, the extensive crosstalk between MAPK and NF-κB pathways and their essential roles in normal tissue homeostasis present significant therapeutic challenges, including the potential for systemic toxicity and the development of compensatory resistance mechanisms [5]. (Sources: [1] Pearson et al., 2001, Endocrine Reviews; [2] Hayden & Ghosh, 2008, Cell; [3] Zhang & Liu, 2002, Cell Research; [4] Dhillon et al., 2007, Oncogene; [5] Taniguchi & Karin, 2018, Seminars in Immunology).

Other names

MAPK/NF-kappaB pathwayMitogen-activated protein kinase/Nuclear factor-kappa B signalingMAPK-NF-kB crosstalkMAPK/NF-kB signaling cascade

Inhibition of mitogen-activated protein kinase kinases (MEK), inhibition of v-raf murine sarcoma viral oncogene homolog B1 (BRAF), or inhibition of the 26S proteasome to prevent the degradation of IκB proteins, thereby sequestering NF-κB in the cytoplasm and preventing its transcriptional activity.