Identification and characterization of an I kappa B kinase
Identification and characterization of an I kappa B kinase
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DOI：
10.1016/s0092-8674(00)80344-x
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发表时间：
1997-07-25
期刊：
影响因子：
64.5
通讯作者：
Rothe, M
中科院分区：
文献类型：
--
作者：
Regnier, CH;Song, HY;Rothe, M
肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）激活转录因子NF-κ B B需要NF-κ B诱导激酶（NIK）。在酵母双杂交筛选NIK相互作用蛋白中，我们已经确定了以前称为CHUK的蛋白激酶。CHUK的过表达激活NF-κ B依赖性报告基因。CHUK的无催化活性突变体是TNF-、IL-1-、TRAF-和NIK诱导的NF-κ B活化的显性负性抑制剂。在哺乳动物细胞中，CHUK与NF-κ B抑制蛋白I κ B-α相关。CHUK特异性磷酸化丝氨酸32和丝氨酸36上的I κ B-α，这是通过泛素-蛋白酶体途径靶向降解I κ B-α所需的修饰。这种I κ B-α的磷酸化通过NIK共刺激大大增强。因此，CHUK是一种将TNF-和IL-1诱导的激酶级联与NF-κ B活化相联系的NK活化的I κ B-α激酶。
Activation of the transcription factor NF-kappa B by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-kappa B-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappa B-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappa B activation. CHUK associates with the NF-kappa B inhibitory protein, I kappa B-alpha, in mammalian cells. CHUK specifically phosphorylates I kappa B-alpha on both serine 32 and serine 36, modifications that are required for targeted degradation of I kappa B-alpha via the ubiquitin-proteasome pathway. This phosphorylation of I kappa B-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated I kappa B-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappa B activation.