IκB激酶结构和功能研究进展

Advances in structure and function of IκB kinase

关键词:  IκB激酶（IKK）  NF-κB  IκB  细胞凋亡  肿瘤发生

Key words:  KK(IκB kinase )  NF-κB  IκB  apoptosis  tumorigenesis

摘要:

在哺乳动物中，核转录因子NF-κB家族包括五个成员：NF-κB1 (p105/p50), NF-κB2 (p100/p52),RelA (p65), RelB, and c-Rel。它们调控与炎症反应，细胞增殖分化及凋亡相关基因的表达。IKK（IκB激酶）是一个蛋白激酶复合体，属于丝/苏氨酸激酶，在核转录因子的活化过程中起着重要的作用。外部刺激因子通过激活IκB激酶（IKK），引起核转录因子的抑制蛋白IκB磷酸化，泛素化和降解，从而使核转录因子活化，进入细胞核内，调节相应基因的转录。此外，有很多研究也表明，IKK的组成性活化和细胞的恶性转化有密切关系。目前已经发现并克隆出了细胞因子诱导的IKK复合体的四个主要组分：IKKα、IKKβ、IKKγ和IKAP。本文综述了IKK的结构、功能，及其与肿瘤发病的关系。

Abstract:

NF-kappaB is a transcription factor of eukaryote, comprising five members in mammals-NF-κB1 (p105/p50), NF-κB2 (p100/p52),RelA (p65), RelB, and c-Rel. NF-kappaB takes part in the expression of numerous cytokines and adhesion molecules which are critical elements involved in the regulation of inflammatory reaction, cell proliferation ,differentiation and apoptosis. IKK(IκB kinase ) is a protein kinase complex,belonging to serine/threonine kinase which plays a key role in the activation of NF-kappaB. Stimulating factors make the IκB phosphorylation, ubiquitilation,and degradation by activating IKK,resulting in NF-kappaB activation. Then NF-κB translocates to the nucleus and regulates target gene transcription. In addition,there are many researches have showed that the composed activation of IKK is very closed associated with cell malignant transformation. Cytokine induced IKK complex comprises 4 main components:IKKα,IKKβ,IKKγ and IKAP. This article reviews the structure, function and the relationship to the tumorigenesis of the IKK.