Figure 7.

Model for FOXO-mediated control of cellular ROS levels. During periods of increased oxidative stress, FOXO4 is activated by Ral- and JNK-mediated phosphorylation on T447 and T451. Increased activity of FOXO4 will lead to induction of transcription of the antioxidant enzymes MnSOD and catalase, leading to a decrease of ROS levels. Thus, activation of FOXO4 by oxidative stress is part of a negative feedback loop to reduce the levels of ROS in a cell. Growth factors can balance cellular ROS through the activation of PKB or JNK, depending on the magnitude and kinetics of PKB and JNK activation. Cellular ROS can be increased through a variety of events including cellular metabolism and various forms of damage (DNA, protein).