Mustard NPR1, a mammalian IkappaB homologue inhibits NF-kappaB activation in human GBM cell lines.
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.
Kesanakurti
Divya
D
Department of Plant Sciences, University of Hyderabad, Hyderabad, India.
Sareddy
Gangadhara Reddy
GR
Babu
Phanithi Prakash
PP
Kirti
Pulugurtha Bharadwaja
PB
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000628:therapy; D008969:Molecular Sequence Data; D009149:Mustard Plant / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D019892:eIF-2 Kinase / Q000378:metabolism
D019938:Cyclin D1; D051546:Cyclooxygenase 2; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D010940:Plant Proteins; D051571:Protein Kinase C-alpha; D016271:Proto-Oncogene Proteins c-myc; D019892:eIF-2 Kinase; C489427:MYC protein, human; C496540:PTGS2 protein, human