The transcription factor SKN-1 regulates responses to oxidants and electrophiles. We previously identified WDR-23 as a repressor of SKN-1. Loss of
wdr-23 causes accumulation of SKN-1, induction of detoxification genes, resistance to oxidants and electrophiles, and increased longevity. Loss of
wdr-23 also slows growth and reduces brood size suggesting that SKN-1 activation may have important consequences. Here, we identify over 800 genes upregulated in
wdr-23(
tm1817) worms, the majority of which are suppressed by
skn-1(RNAi). We also demonstrate that stress resistance, longevity, and reproduction phenotypes of
wdr-23(
tm1817) are completely suppressed by a
skn-1 deletion allele suggesting that the primary function of WDR-23 is to tightly regulate SKN-1. We conducted Gene Set Enrichment Analysis for 26 previously published gene sets regulated by a variety of stress and longevity pathways. Gene sets previously reported to be
skn-1 dependent during stress were among the most strongly enriched for upregulation in our
skn-1 dependent
wdr-23 expression data set indicating that loss of
wdr-23 mimics transcriptional changes induced by SKN-1 during stress. Surprisingly, the gene set with the third greatest enrichment for upregulation in our data set was upregulation in
dpy-10(
e128). DPY-10 is a cuticle collagen and
dpy-10(
e128) alters cuticle structure. Interestingly, many of the overlapping genes the
wdr-23 and
dpy-10 data sets were previously shown to be required for molting. We have confirmed upregulation of a subset of these molting genes in
wdr-23(
tm1817) worms and preliminary experiments suggest that
wdr-23 is required for normal cuticle function. In addition to disrupting cuticle formation,
dpy-10(
e128) was previously reported to constitutively activate osmotic stress responses; several detoxification genes are also upregulated in
dpy-10(
e128) worms. Taken together, these data suggest functional interactions between the cuticle and the xenobiotic responsive SKN-1/WDR-23 pathway. This work is funded by NSF grant IOS-1120130.