Mustard NPR1, a mammalian IκB homologue inhibits NF-κB activation in human GBM cell lines

NF-kappa B activity is tightly regulated by I kappa B class of proteins. I kappa B proteins possess ankyrin repeats for binding to and inhibiting NF-kappa B. The regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with sequence similarity to I kappa B alpha subgroup. Therefore, we examined whether stably expressed BjNPR1 could function as I kappa B in inhibiting NF-kappa B in human glioblastoma cell lines. We observed that BjNPR1 bound to NF-kappa B and inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated the NF-kappa B target genes iNOS, Cox-2, c-Myc and cyclin D1 and reduced the proliferation rate of U373 cells. Finally, BjNPR1 decreased the levels of pERK, pJNK and PKC alpha and increased the Caspase-3 and Caspase-8 activities. These results suggested that inhibition of NF-kappa B activation by BjNPR1 can be a promising therapy in NF-kappa B dependent pathologies. (C) 2009 Elsevier Inc. All rights reserved.