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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Amino Acid Sequence
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Ankyrin Repeat
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Cell Line, Tumor
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Cell Proliferation
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Cyclin D1 / genetics
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Cyclooxygenase 2 / genetics
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Down-Regulation
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Gene Expression
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Gene Expression Regulation
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Genes, Reporter
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Humans
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism*
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Inflammation / therapy
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Molecular Sequence Data
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Mustard Plant / genetics
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Mustard Plant / metabolism*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Neoplasms / therapy
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Nitric Oxide Synthase Type II / genetics
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Plant Proteins / genetics
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Plant Proteins / metabolism*
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Protein Kinase C-alpha / metabolism
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Proto-Oncogene Proteins c-myc / genetics
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eIF-2 Kinase / metabolism
Substances
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I-kappa B Proteins
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MYC protein, human
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NF-kappa B
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Plant Proteins
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Proto-Oncogene Proteins c-myc
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Cyclin D1
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human
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PERK kinase
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eIF-2 Kinase
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Protein Kinase C-alpha