Fig. 1: Identification and validation of Cyclosporin A (CsA) as a chemical inducer of targeted NRF2 protein degradation.
From: PPIA dictates NRF2 stability to promote lung cancer progression
A Representative immunoblot analysis of NRF2 protein levels in nuclear extracts of 17 NSCLC cell lines. B Dot plot showing the relative nuclear NRF2 protein levels in cell lines with KEAP1 and/or KRAS co-mutations (n = 9 cell lines) and in cell lines with KEAP1 and KRAS WT (n = 8 cell lines) related to Fig. 1A. C Overview of the DsRed-IRES-EGFP-NRF2 (RIG-NRF2) screen. CMV, CMV promoter; IRES, Internal ribosome entry site. D Flow cytometry analysis of DsRed and EGFP levels of A549-RIG-NRF2 cells treated with CHX (10 μM), MG132 (10 μM), Ki696 (1 μM), ML334 (50 μM) and CsA (10 μM). The gating strategy are provided in Supplementary Fig. 13. E IC50 values of CsA against a panel of NSCLC cell lines with distinct genetic profile. F Representative immunoblot analysis of NRF2 protein levels in a panel of NSCLC cells upon CsA treatment (10 μM). The results of panels (A, D and F) are representative of three independent experiments. E represents mean ± SD of three independent experiments. P value was analyzed using Two-tailed unpaired Student’s t-test, P < 0.05 was considered statistically significant. Source data are provided as a Source Data file.
