Embryonic lethality, liver degeneration, and impaired NF-κB activation in IKK-β-deficient mice
Embryonic lethality, liver degeneration, and impaired NF-κB activation in IKK-β-deficient mice
复制标题
DOI：
10.1016/s1074-7613(00)80042-4
复制
发表时间：
1999-04-01
期刊：
影响因子：
32.4
通讯作者：
Goeddel, DV
中科院分区：
文献类型：
--
作者：
Tanaka, M;Fuentes, ME;Goeddel, DV
I κ B激酶-α和-β（IKK-α和IKK-β），IKK复合物的催化亚基，磷酸化特定丝氨酸残基上的I κ B蛋白，从而靶向I κ B降解并激活转录因子NF-κ B。为了阐明IKK-β的体内功能，我们产生了IKK-β缺陷小鼠。纯合子小鼠胚胎在妊娠14.5天左右死于肝变性和细胞凋亡。IKK-β缺陷的胚胎成纤维细胞具有降低的基础NF-κ B活性和受损的精氨酸诱导的NF-κ B活化。类似地，IKK-β缺陷细胞中IKK复合物的基础和丝氨酸诱导的激酶活性大大降低。这些结果表明，IKK-β对肝脏发育和NF-κ B活性的调节至关重要，IKK-α只能部分补偿IKK-β的损失。
I kappa B kinase-alpha and -beta (IKK-alpha and IKK-beta), the catalytic subunits of the IKK complex, phosphorylate I kappa B proteins on specific serine residues, thus targeting I kappa B for degradation and activating the transcription factor NF-kappa B. To elucidate the in vivo function of IKK-beta, we generated IKK-beta-deficient mice. The homozygous mouse embryo dies at similar to 14.5 days of gestation due to liver degeneration and apoptosis. IKK-beta-deficient embryonic fibroblasts have both reduced basal NF-kappa B activity and impaired cytokine-induced NF-kappa B 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-kappa B activity and that IKK-alpha can only partially compensate for the loss of IKK-beta.