ASIP COTRAN EARLY CAREER INVESTIGATOR AWARD LECTURE Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases

Maintaining oxygen homeostasis is a most basic cellular process for adapting physiological oxygen variations, and its abnormality typically leads to various disorders in the human body. The key molecules of the oxygen-sensing system include the transcriptional regulator hypoxia-inducible factor (HIF), which controls a wide range of oxygen responsive target genes (eg, EPO and VEGF), certain members of the oxygen/2-oxoglutarate-dependent dioxygenase family, including the HIF proline hydroxylase (PHD, alias EGLN), and an E3 ubiquitin ligase component for HIF destruction called von Hippel-Lindau. In this review, we summarize the physiological role and highlight the pathologic function for each protein of the oxygen-sensing system. A better understanding of their molecular mechanisms of action will help uncover novel therapeutic targets and develop more effective treatment approaches for related human diseases, including cancer.