Characterization of a negative feedback network between SUMO4 expression and NFkappaB transcriptional activity.

Previously, we have demonstrated evidence suggesting that SUMO4 negatively regulates NFκB transcriptional activity, probably through sumoylation of IκBα. Here, we present data indicating that SUMO4 possesses the capacity to conjugate to IκBα. Luciferase reporter assays in 3T3 cells deficient for IκBα further demonstrated that SUMO4 regulates NFκB signaling dependent on its sumoylation of IκBα. More importantly, a putative NFκB binding motif has been characterized within the SUMO4 promoter. Subsequent promoter reporter assays revealed that SUMO4 promoter with disrupted NFκB binding motif failed to response to NFκB specific IL-1β stimulation. ChIP assays showed that NFκB binds to SUMO4 promoter and activates its transcription. Together, our data suggest that SUMO4 may act as a negative feedback regulator to prevent excessive activation of NFκB. Given the importance of NFκB signaling in immune response, SUMO4 could play a role to tightly control the potency of immune response to prevent autoimmunity.