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    Immunity. 1999 Apr;10(4):421-9.

    Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice.

    Tanaka M, Fuentes ME, Yamaguchi K, Durnin MH, Dalrymple SA, Hardy KL, Goeddel DV.

    Tularik, Incorporated, South San Francisco, California 94080, USA.

    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.

    PMID: 10229185 [PubMed - indexed for MEDLINE]

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