FIGURE 8.

Schematic model of SelH-mediated suppression of the senescence response to oxidative stress. SelH is a dual function nuclear protein. First, SelH may serve as an antioxidant through the CXXU motif to directly clear ROS, especially H₂O₂ (24). Second, de novo synthesis of GSH and phase II detoxification enzymes may be transactivated by pNrf2 and SelH through the A-T hook motif (27), when Nrf2 is phosphorylated and dissociated from Keap1 and translocated to the nucleus under oxidative stress. Collectively, SelH protects the nucleus from an ATM- and p53-dependent senescent response to oxidative stress.