DDRGK1 Regulates NF-κB Activity by Modulating IκBα Stability

NF-kappa B is a ubiquitously expressed transcription factor that regulates a large number of genes in response to diverse physiological and pathological stimuli. The regulation of the transcriptional activity of NF-kappa B is often dependent on its interaction with I kappa B alpha. Proteins that bind to I kappa B alpha are critical regulators of NF-kappa B activity. DDRGK1 is a member of the DDRGK domain-containing protein family with unknown function. In this study, we showed that the depletion of DDRGK1 inhibits cell proliferation and invasion. Microarray analysis indicated that the expression of NF-kappa B target genes showed the most significant decrease after depleting of DDRGK1, suggesting that DDRGK1 may play an important role in the NF-kappa B signaling pathway. We further demonstrated that DDRGK1 interacts with I kappa B alpha and regulates its stability, thereby regulates the NF-kappa B transcriptional activity. Our findings identify DDRGK1 as an important regulator of the NF-kappa B pathway.