Mendelian diseases of dysregulated canonical NF-κB signaling: From immunodeficiency to inflammation

Journal of Leukocyte Biology
Oskar Schnappauf, Ivona Aksentijevich

Abstract

NF-κB is a master transcription factor that activates the expression of target genes in response to various stimulatory signals. Activated NF-κB mediates a plethora of diverse functions including innate and adaptive immune responses, inflammation, cell proliferation, and NF-κB is regulated through interactions with IκB inhibitory proteins, which are in turn regulated by the inhibitor of κB kinase (IKK) complex. Together, these 3 components form the core of the NF-κB signalosomes that have cell-specific functions which are dependent on the interactions with other signaling molecules and pathways. The activity of NF-κB pathway is also regulated by a variety of post-translational modifications including phosphorylation and ubiquitination by Lys63, Met1, and Lys48 ubiquitin chains. The physiologic role of NF-κB is best studied in the immune system due to discovery of many human diseases caused by pathogenic variants in various proteins that constitute the NF-κB pathway. These disease-causing variants can act either as gain-of-function (GoF) or loss-of-function (LoF) and depending on the function of mutated protein, can cause either immunodeficiency or systemic inflammation. Typically, pathogenic missense variants act as GoF and the...Continue Reading

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Citations

Oct 22, 2020·PeerJ·Wanwan CaiWuzhou Yuan
Sep 19, 2020·The Journal of Infectious Diseases·Alon Schneider HaitTrine H Mogensen

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