Genetic Diseases Affecting Ubiquitination Processes in NF-κB Signaling

Activation of NF-κB signaling pathways requires ubiquitination processes controlled by a collection of E3 ligases and deubiquitinases. More specifically, modifications by K63- and linear-linked polyubiquitin chains allow the recruitment and activation of essential kinases such as TAK1 and IKK1/IKK2. Human pathologies linked to impaired ubiquitination were recently identified with mutations affecting LUBAC, the main E3 complex catalyzing linear chain formation; TRAF6, a key regulator in immunity and skin appendages development; and CYLD, a deubiquitinase negatively regulating the NF-κB activation process at several levels. They provide an alternative entry point to analyze the consequences of deregulated NF-κB activity.