Li Q, Van Antwerp D, Mercurio F, Lee K F, Verma I M
Salk Institute, La Jolla, CA 92037, USA. Signal Pharmaceuticals, San Diego, CA 92121, USA.
Science. 1999 Apr 9;284(5412):321-5. doi: 10.1126/science.284.5412.321.
Phosphorylation of inhibitor of kappa B (IkappaB) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta). 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-alpha (TNF-alpha)- and interleukin-1alpha-induced NF-kappaB activity and an enhanced apoptosis in response to TNF-alpha. IKK1 associated with NF-kappaB essential modulator (IKKgamma/IKKAP1), another component of the IKK complex. These results show that IKK2 is essential for mouse development and cannot be substituted with IKK1.
IκB（核因子κB抑制蛋白）蛋白的磷酸化是转录核因子κB（NF-κB）激活过程中的重要一步，这需要两种IκB激酶，即IKK1（IKKα）和IKK2（IKKβ）。缺乏IKK2基因的小鼠因细胞凋亡而出现广泛的肝脏损伤，并在胚胎期死亡，但这些小鼠可通过使编码肿瘤坏死因子受体1的基因失活而得到挽救。从IKK2基因敲除胚胎中分离出的小鼠胚胎成纤维细胞显示，肿瘤坏死因子-α（TNF-α）和白细胞介素-1α诱导的NF-κB活性显著降低，并且对TNF-α的凋亡反应增强。IKK1与IKK复合物的另一个组分NF-κB必需调节因子（IKKγ/IKKAP1）相关。这些结果表明，IKK2对小鼠发育至关重要，且不能被IKK1替代。
