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Sci. STKE, 11 July 2000
Vol. 2000, Issue 40, p. tw7
[DOI: 10.1126/stke.2000.40.tw7]


Apoptosis Protection from Apoptosis by GSK-3β

Glycogen synthase kinase-3α and -3β (GSK-3α, -β) have established roles as serine kinases in regulating the Wnt signaling pathway. Hoeflich et al. knocked out the GSK-3β gene in mice and found that the embryos died from severe liver degeneration that could be prevented by treatment of the pregnant mice with anti-TNF-α antibodies. It is surprising that the mice do not appear to have defects in Wnt signaling, a finding highlighted in the accompanying article by Pomerantz and Baltimore. Analysis of cultured cells from the knockout mice showed that the cells were hypersensitive to TNF-α-induced apoptosis because of reduced activation of NF-{kappa}B. The defect in NF-{kappa}B signaling appeared to occur downstream of degradation of I-{kappa}B and nuclear translocation of NF-{kappa}B, because both of these events occurred with kinetics identical to those in wild-type cells. The defect in NF-{kappa}B signaling was also specific to the regulation of certain genes because expression of E-selectin was reduced, but expression of I-{kappa}B was unaffected, in the knockout cells. Thus, GSK-3β may play a role in controlling the transcriptional activity of NF-{kappa}B within the nucleus in a gene-specific manner.

Hoeflich, K.P., Luo, J., Rubie, E.A., Tsao, M.-S., Jin, O., and Woodgett, J.R. (2000) Requirement for glycogen synthase kinase-3β in cell survival and NF-{kappa}B activation. Nature 406: 86-90. [Online Journal]

Pomerantz, J.L., and Baltimore, D. (2000) A cellular rescue team. Nature 406: 26-28. [Online Journal]

Citation: Protection from Apoptosis by GSK-3β. Sci. STKE 2000, tw7 (2000).

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