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. 2017 Apr 28;13(4):e1006762. doi: 10.1371/journal.pgen.1006762

Fig 1. WDR23 influences cytoprotective pathways via regulation of NRF2.

Fig 1

(A) Schematic of the domains found in human WDR23 isoform 1 (pink) and WDR23 isoform 2 (orange). (B,C) Representative images of HEK-293T cells overexpressing mCherry:LAMIN and either GFP:WDR23 isoform 1 (B) or GFP:WDR23 isoform 2 (C). Scale bar, 20μm. (D) Overexpression of WDR23 isoform 1 or WDR23 isoform 2 reduces the expression of an ARE-inducible luciferase reporter as compared to control (GFP expression) (Control n = 32, Iso 1 n = 24, Iso 2 n = 24). (E-H) Cells expressing WDR23 have reduced levels of the NRF2 target genes GSTA1 (Control n = 9, Iso 1 n = 6, Iso 2 n = 3) (E), CYP3A4 (Control n = 9, Iso 1 n = 6, Iso 2 n = 3) (F), ACADL (Control n = 12, Iso 1 n = 9, Iso 2 n = 9) (G), and ACADM (Control n = 12, Iso 1 n = 9, Iso 2 n = 9) (H) as compared to control (GFP expression). (I-M) Overexpression of WDR23 abrogates the effects of tBHQ-treatment on NRF2 targets GSR (Control n = 9, +tBHQ n = 9, Iso 1 n = 6, Iso 1 +tBHQ n = 6, Iso 2 n = 3, Iso 2 +tBHQ n = 3) (I), CYP1A1 (Control n = 9, +tBHQ n = 9, Iso 1 n = 6, Iso 1 +tBHQ n = 6, Iso 2 n = 3, Iso 2 +tBHQ n = 3) (J), CPT1A1 (Control n = 12, +tBHQ n = 12, Iso 1 n = 9, Iso 1 +tBHQ n = 9, Iso 2 n = 9, Iso 2 +tBHQ n = 9) (K), ACADS (Control n = 12, +tBHQ n = 12, Iso 1 n = 9, Iso 1 +tBHQ n = 9, Iso 2 n = 9, Iso 2 +tBHQ n = 9) (L), and ACADL (Control n = 12, +tBHQ n = 12, Iso 1 n = 9, Iso 1 +tBHQ n = 9, Iso 2 n = 9, Iso 2 +tBHQ n = 9) (M) as compared to control (GFP overexpression). Wdr23 knockout MEF cells have increased levels of the NRF2 target genes Gclm (Control n = 5, KO n = 12) (N), Nqo1 (Control n = 5, KO n = 12) (O), and Gsr (Control n = 5, KO n = 12) (P). Data are mean ± s.e.m.; (D) two-tailed t-test relative to control samples; (E-P) one-tailed t-test relative to control samples. *P<0.05, **P<0.01, ***P<0.001.