Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization
Vettori A., Greenald D., Wilson GK., Peron M., Facchinello N., Markham E., Sinnakaruppan M., Matthews LC., McKeating JA., Argenton F., van Eeden FJM.
Significance An in vivo chemical screen in zebrafish identified glucocorticoids (GCs) as activators of hypoxia-inducible factor transcriptional responses in the liver. This cross-talk is conserved in human liver and requires glucocorticoid receptor signaling but not DNA binding. In human liver cells, GCs down-regulate Von Hippel Lindau expression at a posttranscriptional level most likely through c-src–mediated proteasomal degradation. Since the liver is an important regulator of blood glucose and hypoxia-inducible factors regulate gluconeogenesis/glycogen synthesis, cross-talk between these transcriptional regulators may be essential to control glucose metabolism in the liver. This identified, conserved, noncanonical pathway may have wider physiological significance in health and disease.