Abstract
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.
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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Crosses, Genetic
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Female
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Fetal Death / enzymology
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Fetal Death / genetics
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Fetal Death / immunology*
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Humans
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I-kappa B Kinase
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Interleukin-6 / biosynthesis
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JNK Mitogen-Activated Protein Kinases
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Liver / embryology*
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Liver / pathology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitogen-Activated Protein Kinases*
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NF-kappa B / metabolism*
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Protein Serine-Threonine Kinases / deficiency*
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Protein Serine-Threonine Kinases / genetics*
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Transfection / immunology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / pharmacology
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Tumor Necrosis Factor-alpha / physiology
Substances
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Interleukin-6
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NF-kappa B
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Tumor Necrosis Factor-alpha
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Protein Serine-Threonine Kinases
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CHUK protein, human
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Chuk protein, mouse
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Ikbkb protein, mouse
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Ikbke protein, mouse
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases