NFKB1 and viral infectious disease: For example, NLRP4 recruits the E3 ligase DTX4 to promote the ubiquitination and degradation of TBK1, a key kinase that activates both IRF3 and NF-κB.190 Similarly, Triad3A catalyzes the K48-linked polyUb of TRAF3,191 whereas RNF5 mediates the K48-linked ubiquitination and degradation of MAVS itself.192 These ubiquitination events collectively serve as critical checkpoints to prevent excessive NF-κB activation, ensuring a balanced immune response to viral infections (Fig. 3).