Reptin Physically Interacts with P65 and Represses NF-κB Activation.

Reptin and Pontin belong to the AAA+ ATPase family of DNA helicases. Both proteins are present in several chromatin-remodeling machineries and are involved in transcriptional regulation, DNA repair, and telomerase activity, but they also function independently from each other. Here we report the identification of p65 as an interacting partner of Reptin. Using reporter gene assays, we show Reptin inhibits NF-κB transactivation after TNFα stimulation. Reptin is mainly localized in the cytoplasm and impedes NF-κB activation by inhibiting IκB-α degradation and restraining p65 nuclear translocation. These results reveal a novel mechanism for the control of NF-κB pathway by cytoplasmic Reptin.