Page Angustias, Navarro Manuel, Suárez-Cabrera Cristian, Bravo Ana, Ramirez Angel
Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), 28040 Madrid, Spain.
Oncogenomic Unit, Institute of Biomedical Investigation "12 de Octubre i+12", 28041 Madrid, Spain.
Genes (Basel). 2017 Dec 8;8(12):376. doi: 10.3390/genes8120376.
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is a kinase principally known as a positive regulator of the ubiquitous transcription factor family Nuclear Factor-kappa B (NF-κB). In addition, IKKβ also phosphorylates a number of other proteins that regulate many cellular processes, from cell cycle to metabolism and differentiation. As a consequence, IKKβ affects cell physiology in a variety of ways and may promote or hamper tumoral transformation depending on hitherto unknown circumstances. In this article, we give an overview of the NF-κB-dependent and -independent functions of IKKβ. We also summarize the current knowledge about the relationship of IKKβ with cellular transformation and cancer, obtained mainly through the study of animal models with cell type-specific modifications in IKKβ expression or activity. Finally, we describe the most relevant data about IKKβ implication in cancer obtained from the analysis of the human tumoral samples gathered in The Cancer Genome Atlas (TCGA) and the Catalogue of Somatic Mutations in Cancer (COSMIC).
核因子κB激酶亚基β(IKKβ)是一种激酶,主要作为普遍存在的转录因子家族核因子κB(NF-κB)的正向调节因子为人所知。此外,IKKβ还能磷酸化许多其他蛋白质,这些蛋白质调节从细胞周期到代谢和分化等众多细胞过程。因此,IKKβ以多种方式影响细胞生理,并且根据迄今未知的情况,可能促进或阻碍肿瘤转化。在本文中,我们概述了IKKβ依赖于NF-κB和不依赖于NF-κB的功能。我们还总结了目前关于IKKβ与细胞转化和癌症关系的知识,这些知识主要通过对IKKβ表达或活性进行细胞类型特异性修饰的动物模型研究获得。最后,我们描述了从癌症基因组图谱(TCGA)和癌症体细胞突变目录(COSMIC)中收集的人类肿瘤样本分析中获得的关于IKKβ与癌症关联的最相关数据。