Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2000-07

AUTHORS

Klaus P. Hoeflich, Juan Luo, Elizabeth A. Rubie, Ming-Sound Tsao, Ou Jin, James R. Woodgett

ABSTRACT

Glycogen synthase kinase-3 (GSK-3)-α and -β are closely related protein-serine kinases, which act as inhibitory components of Wnt signalling during embryonic development and cell proliferation in adult tissues1,2. Insight into the physiological function of GSK-3 has emerged from genetic analysis in Drosophila3,4, Dictyostelium 5 and yeast6,7. Here we show that disruption of the murine GSK-3β gene results in embryonic lethality caused by severe liver degeneration during mid-gestation, a phenotype consistent with excessive tumour necrosis factor (TNF) toxicity, as observed in mice lacking genes involved in the activation of the transcription factor activation NF-κB. GSK-3β-deficient embryos were rescued by inhibition of TNF using an anti-TNF-α antibody. Fibroblasts from GSK-3β-deficient embryos were hypersensitive to TNF-α and showed reduced NF-κB function. Lithium treatment (which inhibits GSK-3; refs 8, 9) sensitized wild-type fibroblasts to TNF and inhibited transactivation of NF-κB. The early steps leading to NF-κB activation (degradation of I-κB and translocation of NF-κB to the nucleus) were unaffected by the loss of GSK-3β, indicating that NF-κB is regulated by GSK-3β at the level of the transcriptional complex. Thus, GSK-3β facilitates NF-κB function. More... »

PAGES

86-90

Journal

TITLE

Nature

ISSUE

6791

VOLUME

406

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/35017574

    DOI

    http://dx.doi.org/10.1038/35017574

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044051571

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10894547


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