The Role Of Vab-3 in the Caenorhabditis Elegans Oxidative Stress Response

The oxidative stress response protects the cell by balancing the number of free radicals inside the cell. BRAP2 is a Ras effector with ubiquitin ligase activity and conserved in C. elegans. Our lab has previously shown that C. elegans BRAP-2 is a negative regulator of SKN-1/Nrf2 that activates ROS detoxifying enzymes, and vab-3/PAX6 RNAi induction in brap-2 mutants reduced basal expression levels of gst-4. Based on the link between SKN-1 and BRAP-2, I examined the role of VAB-3 in the oxidative stress response. I found that a loss of vab-3 caused decreased basal expression levels of gst-4 in brap-2; vab-3 double mutants, decreased expression levels of gst-4, sdz-8, ugt-13 and ctl-1 and increased mortality rates toward oxidative stress in C. elegans. Moreover, I found that VAB-3 together with SKN-1 synergistically enhanced activities of gst-4 and skn-1c promoters. Thus, VAB-3 contributes to the oxidative stress response through the SKN-1/Nrf2 pathway.