Mustard NPR1, a mammalian IkappaB homologue inhibits NF-kappaB activation in human GBM cell lines

Abstract

NF-kappaB activity is tightly regulated by IkappaB class of proteins. IkappaB proteins possess ankyrin repeats for binding to and inhibiting NF-kappaB. The regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with sequence similarity to IkappaBalpha subgroup. Therefore, we examined whether stably expressed BjNPR1 could function as IkappaB in inhibiting NF-kappaB in human glioblastoma cell lines. We observed that BjNPR1 bound to NF-kappaB and inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated the NF-kappaB 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 PKCalpha and increased the Caspase-3 and Caspase-8 activities. These results suggested that inhibition of NF-kappaB activation by BjNPR1 can be a promising therapy in NF-kappaB dependent pathologies.