Severe Liver Degeneration in Mice Lacking the I kappa B Kinase 2 Gene

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Abstract

Phosphorylation of inhibitor of kappa B (I kappa B) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-kappa B) and requires two I kappa B kinases, IKK1 (IKK[small alpha, Greek]) and IKK2 (IKK[small beta, Greek]). Mice that are devoid of the IKK2 gene had extensive liver damage from apoptosis and died as embryos, but these mice could be rescued by the inactivation of the gene encoding tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were isolated from IKK2-/- embryos showed a marked reduction in tumor necrosis factor-[small alpha, Greek] (TNF-[small alpha, Greek])- and interleukin-1[small alpha, Greek]-induced NF-kappa B activity and an enhanced apoptosis in response to TNF-[small alpha, Greek]. IKK1 associated with NF-kappa B essential modulator (IKK[small gamma, Greek]/IKKAP1), another component of the IKK complex. These results show that IKK2 is essential for mouse development and cannot be substituted with IKK1.

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