YAP, A Component of the Hippo Pathway, is Essential for Antioxidant Defense

The highly conserved Hippo signaling pathway which negatively regulates cell growth and survival is a key regulator of organ size and tumorigenesis. Emerging evidence suggests the important role of Hippo pathway in response to oxidative stress. However the mechanism was rarely explored. Here we reported that YAP protein, which is the terminal effector of Hippo signaling pathway, shuttled between cytoplasm and nucleus following different concentration of sodium arsenite treatment, thereby controlling cell death or survival under arsenite-induced oxidative stress. Low concentration of sodium arsenite inhibited phosphorylation of YAP S127 and promoted YAP translocation to nucleus, thus further enhanced cell proliferation. However, high concentration of sodium arsenite augmented phosphorylation of YAP at S127 and induced translocation of YAP into cytoplasm and further caused cell apoptosis. These results suggest that YAP translocation plays an important role in deciding cell fate under arsenite-induced oxidative stress.