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

Previously, we have demonstrated evidence suggesting that SUMO4 negatively regulates NFkappaB transcriptional activity, probably through sumoylation of IkappaBalpha. Here, we present data indicating that SUMO4 possesses the capacity to conjugate to IkappaBalpha. Luciferase reporter assays in 3T3 cells deficient for IkappaBalpha further demonstrated that SUMO4 regulates NFkappaB signaling dependent on its sumoylation of IkappaBalpha. More importantly, a putative NFkappaB binding motif has been characterized within the SUMO4 promoter. Subsequent promoter reporter assays revealed that SUMO4 promoter with disrupted NFkappaB binding motif failed to response to NFkappaB specific IL-1beta stimulation. ChIP assays showed that NFkappaB 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 NFkappaB. Given the importance of NFkappaB signaling in immune response, SUMO4 could play a role to tightly control the potency of immune response to prevent autoimmunity.