Scheidereit Claus
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Oncogene. 2006 Oct 30;25(51):6685-705. doi: 10.1038/sj.onc.1209934.
Transcription factors of the NF-kappaB family regulate hundreds of genes in the context of multiple important physiological and pathological processes. NF-kappaB activation depends on phosphorylation-induced proteolysis of inhibitory IkappaB molecules and NF-kappaB precursors by the ubiquitin-proteasome system. Most of the diverse signaling pathways that activate NF-kappaB converge on IkappaB kinases (IKK), which are essential for signal transmission. Many important details of the composition, regulation and biological function of IKK have been revealed in the last years. This review summarizes current aspects of structure and function of the regular stoichiometric components, the regulatory transient protein interactions of IKK and the mechanisms that contribute to its activation, deactivation and homeostasis. Both phosphorylation and ubiquitinatin (destructive as well as non-destructive) are crucial post-translational events in these processes. In addition to controlling induced IkappaB degradation in the cytoplasm and processing of the NF-kappaB precursor p100, nuclear IKK components have been found to act directly at the chromatin level of induced genes and to mediate responses to DNA damage. Finally, IKK is engaged in cross talk with other pathways and confers functions independently of NF-kappaB.
NF-κB家族的转录因子在多种重要的生理和病理过程中调控着数百个基因。NF-κB的激活依赖于泛素-蛋白酶体系统对抑制性IκB分子和NF-κB前体进行磷酸化诱导的蛋白水解。激活NF-κB的多种信号通路大多汇聚于IκB激酶（IKK），IKK对信号传递至关重要。近年来，IKK的组成、调控及生物学功能的许多重要细节已被揭示。本综述总结了IKK常规化学计量组分的结构和功能、IKK的调控性瞬时蛋白相互作用以及促成其激活、失活和稳态的机制等当前研究内容。磷酸化和泛素化（包括破坏性和非破坏性的）在这些过程中都是关键的翻译后事件。除了控制细胞质中诱导型IκB的降解以及NF-κB前体p100的加工外，还发现核IKK组分可直接作用于诱导基因的染色质水平并介导对DNA损伤的反应。最后，IKK与其他通路存在相互作用，且能独立于NF-κB发挥功能。
