Summary of interactions between the endoplasmic reticulum (ER) unfolded protein response (UPR) and antioxidant/detoxification transcription factor SKN-1 in <i>C. elegans</i>.

<p>The ER folds and modifies newly synthesized membrane and secreted proteins. Accumulation of misfolded proteins in the ER activates three canonical branches of the UPR, which are mediated by XBP-1, PEK-1, and ATF-6 (mammalian homologs in parentheses). Transcriptional targets of the UPR function to promote protein folding and covalent modification of new proteins and degradation of misfolded proteins. SKN-1 (homolog of mammalian proteins Nrf1, Nrf2, and Nrf3) was found to transcriptionally regulate core UPR regulators and some downstream targets during ER stress <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003827#pgen.1003827-GloverCutter1" target="_blank">[1]</a>. Core UPR regulators also transcriptionally regulate SKN-1 during ER stress and oxidative/xenobiotic stress <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003827#pgen.1003827-GloverCutter1" target="_blank">[1]</a>. Based on studies in mammalian cells <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003827#pgen.1003827-Cullinan2" target="_blank">[12]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003827#pgen.1003827-Cullinan3" target="_blank">[13]</a>, SKN-1 would also be expected to buffer reactive oxygen species that are produced in the ER. A long variant of SKN-1 may reside in the ER membrane (not shown). Regulation of SKN-1 during ER and oxidative/xenobiotic stress may include post-translational modifications.