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​Antioxidant Pathway


NRF2 is a transcription factor, which plays an important role in responding to oxidative stress. Under normal cellular conditions, NRF2 forms a protein complex with Keap1 in the cytoplasm, which results in the proteasomal degradation of NRF2 causing it to be inactive.  Oxidative stress leads to the activation of a number of kinases including MAPK, ERK, p38, PKC, and PI3K.  They phosphorylate both Keap1 and NRF2, which disrupt the Keap1-NRF2 complex, and stimulate the translocation of NRF2 to the nucleus, where it forms a complex with Maf proteins.  The NRF2/Maf heterodimers bind directly to antioxidant response elements (AREs) located within promoters of NRF2 target genes and coordinate the expression of antioxidant gene products. 

Signosis has developed NRF2-reporter stable cell line that has been stably transfected with pTA-NRF2-luciferase reporter vector, which contains 8 repeats of NRF2 binding sites, a minimal promoter upstream of the firefly luciferase coding region, along with a G418 expression vector.  This cell line can be used to investigate oxidative stress-mediated activation of upstream kinases and to screen anticancer drugs that can induce ARE-driven gene expression.



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