REGULATION OF NF-KAPPA-B ACTIVATION BY MAP KINASE CASCADES

Transcription factor NF-kappa B plays a crucial role in the regulation of numerous genes involved in the inflammatory response and control o f cell death. Activation of NF-<kappaB is mediated through the phospho rylation of its inhibitory subunit I kappa B, followed by the subseque nt degradation of I kappa B at the proteasome. A second level of contr ol involves phosphorylation events of NF-kappa B in the cell nucleus. The kinases that regulate these processes are rather undefined. NF-kap pa B activation is induced by a great variety of predominantly pathoge nic and noxious stimuli. A similar spectrum of conditions triggers the activation of two mitogen-activated protein (MAP) kinase cascades, de signated as the JNK and p38 kinase pathways. Several points of evidenc e suggest that MAP kinases can participate in the regulation of NF-kap pa B transcriptional activity. Here, we will review very recent data d emonstrating thai both the JNK and the p38 pathways are involved in th e activation of NF-kappa B in the cytoplasm as well as in modulation o f its transactivating potential in the nucleus.