Fig. 1.

A gain-of-function screen identifies kinases that regulate NRF2-dependent transcription. (A) Volcano plot of kinase overexpression screen of NRF2-driven hQR41-firefly luciferase reporter in HEK293T cells. The experiment was performed in biological triplicate and six technical replicates. NRF2 transcriptional activity was determined by measuring levels of hQR41-firefly luciferase normalized to TK-Renilla luciferase. Data are plotted relative to GFP overexpression control. Significance was measured with Student's t-test including correction for multiple comparison using Benjamini and Hochberg method. Red and green circles indicate candidate kinases that passed an FDR of less than 10%. NRF2, KEAP1and DPP3 serve as positive controls. (B-D) hQR41 reporter validation study for the indicated kinases in HEK293T cells, MEFs and H2228 cells. (E) Venn diagram of validated kinase hits in HEK293T, H2228 and MEFs.