Credit: Frontiers in Immunology/DOI: 10.3389/fimmu.2023.1073608
TBK1 continuously induces the degradation of its cognate kinase IKKepsilon. For this purpose, TBK1 recruits an as yet unidentified cofactor (X) via its scaffold protein TANK, which destabilizes IKKepsilon. Upon infection, both TBK1 and IKKepsilon contribute to the production of interferon (type I IFN). Right: Upon pathogen-induced degradation or genetic loss of TBK1, it no longer reduces IKKepsilon protein stability. Thus, IKKepsilon protein levels are greatly enhanced, which compensates for the deficiency of TBK1. This ensures an unrestrained type I IFN response and efficient clearance of infection.