Regulation of NF-κB activation by MAP kinase cascades

Abstract

Transcription factor NF-κB plays a crucial role in the regulation of numerous genes involved in the inflammatory response and control of cell death. Activation of NF-κB is mediated through the phosphorylation of its inhibitory subunit IκB, followed by the subsequent degradation of IκB at the proteasome. A second level of control involves phosphorylation events of NF-κB in the cell nucleus. The kinases that regulate these processes are rather undefined. NF-κB activation is induced by a great variety of predominantly pathogenic and noxious stimuli. A similar spectrum of conditions triggers the activation of two mitogen-activated protein (MAP) kinase cascades, designated as the JNK and p38 kinase pathways. Several points of evidence suggest that MAP kinases can participate in the regulation of NF-κB transcriptional activity. Here, we will review very recent data demonstrating that both the JNK and the p38 pathways are involved in the activation of NF-κB in the cytoplasm as well as in modulation of its transactivating potential in the nucleus.