Activators of gcs-1 have diverse effects on SKN-1 and expression of other SKN-1 target genes. Some candidate activators act independently or downstream from SKN-1 to increase gcs-1 expression whereas others, such as UFD-2, are required for nuclear SKN-1 levels and arsenite-induced expression of multiple phase 2 detoxification genes. (A) The effect of 14 RNAi that reduce intestinal gcs-1p::gfp expression in prdx-2 mutant and arsenite-treated animals (Table 1) on the levels of a constitutively active form of SKN-1 (SKN-1B/CS393A::GFP) present in intestinal nuclei . RNAi that produced a statistically significant decrease (***P < 0.001) or increase (***P < 0.001; *P < 0.05) in nuclear SKN-1 levels are indicated. The data shown were obtained in three independent experiments. (B) K04G7.11 and apb-3 RNAi significantly increased (***P < 0.001; **P < 0.01) wild-type SKN-1::GFP forms (SKN-1op::GFP)  in two independent experiments (representative experiment is shown). (C) Effect of K04G7.11, apb-3, ufd-2 and thoc-2 RNAi, compared with vector control, on the total gcs-1, gst-4, gst-7, dhs-8 and sdz-8 mRNA levels in animals treated for 30 min with 5 mM sodium arsenite. (D) wdr-23 RNAi causes a similar increase in intestinal expression of gcs-1p::gfp in vector control and ufd-2 RNAi-treated animals. The data shown were obtained in two independent experiments. (E) The survival of L4-larval-stage wild-type and ufd-2 (tm1380) mutant animals on plates containing 7.5 mM sodium arsenite (As3+) was monitored with log-rank analysis indicating that ufd-2 (tm1380) mutant animals are significantly more sensitive to the toxicity of arsenite than wild type (N2) (P < 0.001 in each case). n = 30 to 36.