SEM-4 is a Novel Protein in the BRAP-2/SKN-1/ROS Detoxification Pathway
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Oxidative stress causes damage to cells by creating reactive oxygen species (ROS). The overproduction of ROS is detrimental, having been linked to the onset of premature ageing and age-related diseases. Our lab has previously found that a partial deletion of brap-2 (BRCA-1 associated protein 2) significantly increased the expression of gst-4, a phase II detoxification enzyme in C.elegans. An RNAi screen for 940 transcription factors on a brap-2;gst-4::gfp strain resulted in more than 20 candidates that are proposed to alter expression of gst-4 in BRAP- 2/SKN-1/ROS detoxification pathway, and one of those genes, sem-4, was chosen for the further studies. A significant reduction in gst-4 mRNA levels was observed in sem-4;brap-2 double mutants and sem-4 mutants. We also found that higher levels of ROS were generated in sem-4 mutants in comparison to N2 worms, indicating that SEM-4 is required to prevent overproduction of ROS in vivo. Furthermore, the lifespan of skn-1 overexpressing worms was dependent on presence of sem-4. Next, survival of worms exposed to constant oxidative stress was decreased in sem-4 mutants. Lastly, we determined that SEM-4 is a transcriptional regulator of skn-1c. Together, these results indicate a newly identified role of SEM-4 in regulating expression of phase II detoxification enzymes and preventing the harmful effects caused by overproduction of ROS.