Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice.
IkappaB kinase-alpha and -beta (IKK-alpha and IKK-beta), the catalytic subunits of the IKK complex, phosphorylate IkappaB proteins on specific serine residues, thus targeting IkappaB for degradation and activating the transcription factor NF-kappaB. To elucidate the in vivo function of IKK-beta, we generated IKK-beta-deficient mice. The homozygous mouse embryo dies at approximately 14.5 days of gestation due to liver degeneration and apoptosis. IKK-beta-deficient embryonic fibroblasts have both reduced basal NF-kappaB activity and impaired cytokine-induced NF-kappaB activation. Similarly, basal and cytokine-inducible kinase activities of the IKK complex are greatly reduced in IKK-beta-deficient cells. These results indicate that IKK-beta is crucial for liver development and regulation of NF-kappaB activity and that IKK-alpha can only partially compensate for the loss of IKK-beta.
Pubmed ID: 10229185 RIS Download
Animals | Calcium-Calmodulin-Dependent Protein Kinases | Cell Line | Crosses, Genetic | Enzyme Activation | Female | Fetal Death | Humans | I-kappa B Kinase | Interleukin-6 | JNK Mitogen-Activated Protein Kinases | Liver | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mitogen-Activated Protein Kinases | NF-kappa B | Protein-Serine-Threonine Kinases | Transfection | Tumor Necrosis Factor-alpha