TY - JOUR
T1 - Mustard NPR1, a mammalian IκB homologue inhibits NF-κB activation in human GBM cell lines
AU - Kesanakurti, Divya
AU - Sareddy, Gangadhara Reddy
AU - Babu, Phanithi Prakash
AU - Kirti, Pulugurtha Bharadwaja
N1 - Funding Information:
KD and GRS are thankful to the Council of Scientific and Industrial Research, Government of India for research fellowships.
PY - 2009/12/18
Y1 - 2009/12/18
N2 - NF-κB activity is tightly regulated by IκB class of proteins. IκB proteins possess ankyrin repeats for binding to and inhibiting NF-κB. The regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with sequence similarity to IκBα subgroup. Therefore, we examined whether stably expressed BjNPR1 could function as IκB in inhibiting NF-κB in human glioblastoma cell lines. We observed that BjNPR1 bound to NF-κB and inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated the NF-κB 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 PKCα and increased the Caspase-3 and Caspase-8 activities. These results suggested that inhibition of NF-κB activation by BjNPR1 can be a promising therapy in NF-κB dependent pathologies.
AB - NF-κB activity is tightly regulated by IκB class of proteins. IκB proteins possess ankyrin repeats for binding to and inhibiting NF-κB. The regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with sequence similarity to IκBα subgroup. Therefore, we examined whether stably expressed BjNPR1 could function as IκB in inhibiting NF-κB in human glioblastoma cell lines. We observed that BjNPR1 bound to NF-κB and inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated the NF-κB 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 PKCα and increased the Caspase-3 and Caspase-8 activities. These results suggested that inhibition of NF-κB activation by BjNPR1 can be a promising therapy in NF-κB dependent pathologies.
KW - IκB
KW - Mustard
KW - NF-κB
KW - NPR1
KW - U373
KW - p50
KW - p65
UR - http://www.scopus.com/inward/record.url?scp=70449715125&partnerID=8YFLogxK
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U2 - 10.1016/j.bbrc.2009.09.046
DO - 10.1016/j.bbrc.2009.09.046
M3 - Article
C2 - 19766095
AN - SCOPUS:70449715125
SN - 0006-291X
VL - 390
SP - 427
EP - 433
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -