Moreover, recent studies show that ROS regulates activation of the nuclear transcriptional factor ATF2 by phosphorylated JNK [41] and increases ROS levels activate upstream HIF-1α pathways, such as MAPK signaling, which can in turn induce HIF-1α dependent transcriptional activity in cancer cells and HL1 cardiomyocytes [42]. The gene discussed is MAPK8; the disease is cancer.