caa a22 4500 606175393 CHVBK 20210128100742.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00018-014-1793-y doi (NATIONALLICENCE)springer-10.1007/s00018-014-1793-y IKK-related genetic diseases: probing NF-κB functions in humans and other matters [Elektronische Daten] [Anna Senegas, Jérémie Gautheron, Alice Maurin, Gilles Courtois] The transcription factor NF-κB plays a key role in numerous physiological processes such as inflammation, immunity, cell proliferation or control of cell death. Its activation is tightly controlled by a kinase complex, IκB kinase (IKK), composed of three core proteins: IKK1/IKKα, IKK2/IKKβ and NEMO/IKKγ. The first two are structurally related kinases whereas the third one is a regulatory subunit exhibiting affinity for upstream activators modified by polyubiquitin chains. Over the years, several inherited diseases caused by mutations of each of the three subunits of IKK have been identified in humans together with diseases caused by mutations of several of its substrates. They are associated with very specific and complex phenotypes involving a broad range of abnormalities such as impaired innate and acquired immune response, perturbed skin development and defects of the central nervous system. Here, we summarize the diverse clinical, cellular and molecular manifestations of IKK-related genetic diseases and show that studying patient-related mutations affecting the IKK subunits and some of their substrates offers the opportunity to understand the various functions of NF-κB in humans, complementing studies performed with mouse models. This analysis also provides glimpses about putative functions of IKK subunits that may be NF-κB-independent. Springer Basel, 2014 NF-κB nationallicence IKK nationallicence Genetic diseases nationallicence Immunodeficiencies nationallicence Skin development nationallicence Senegas Anna INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut Gautheron Jérémie Department of Gastroenterology, University Hospital RWTH Aachen, Aachen, Germany aut Maurin Alice INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut Courtois Gilles INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut Cellular and Molecular Life Sciences Springer Basel 72/7(2015-04-01), 1275-1287 1420-682X 72:7<1275 2015 72 18 https://doi.org/10.1007/s00018-014-1793-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1793-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Senegas Anna INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut NATIONALLICENCE 700 1- Gautheron Jérémie Department of Gastroenterology, University Hospital RWTH Aachen, Aachen, Germany aut NATIONALLICENCE 700 1- Maurin Alice INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut NATIONALLICENCE 700 1- Courtois Gilles INSERM U1038, iRTSV, CEA Grenoble, Grenoble, France aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/7(2015-04-01), 1275-1287 1420-682X 72:7<1275 2015 72 18