FIG. 13.

Overview of ROS signaling. Reactive oxygen species (ROS) are generated through external stimuli or stress, as well as metabolic processes, and act as a signal for JNK and ERK1/2 kinases, resulting in the activation of a number of transcription factors, including Egr-1, CREB, and Jun/ATF4, which are involved in the inducible expression of APE1. In melanoma cells, MiTF also was shown to upregulate transcription of APE1. In its role as a redox factor, APE1 reduces a number of transcription factors, including AP-1, Egr-1, NF-κB, p53, CREB, and HIF-1α. Thus, APE1 controls the redox status of several transcription factors that in turn regulate expression of APE1. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).