Previously, we have demonstrated evidence suggesting that SUMO4 negatively regulates NF kappa B transcriptional activity, probably through surnoylation of I kappa B alpha. Here, we present data indicating that SUMo4 possesses the capacity to conjugate to I kappa B alpha. Luciferase reporter assays in 3T3 cells deficient for I kappa B alpha further demonstrated that SUMO4 regulates NF kappa B signaling dependent on its surnoylation of I kappa B alpha. More importantly, a Putative NF kappa B binding motif has been characterized within the SUMO4 promoter. Subsequent promoter reporter assays revealed that SUMO4 promoter with disrupted NF kappa B binding motif failed to response to NF kappa B specific IL-1 beta stimulation. ChIP assays showed that NF kappa B 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 NF kappa B. Given the importance of NF kappa B signaling in immune response, SUMO4 could play a role to tightly control the potency Of immune response to prevent autoimmunity. (C) 2009 Published by Elsevier Inc.