Protein kinase C-δ regulates the stability of hypoxia-inducible factor-1α under hypoxia

Abstract

Hypoxia is a state of deficiency of available oxygen in the blood and tissues, and it occurs during several pathophysiological processes, including tumorigenesis. Under hypoxia, hypoxia-inducible factor-1 (HIF-1) plays an essential role in cellular oxygen homeostasis. In the present article protein kinase C-δ (PKC-δ) is activated by hypoxia, increases the protein stability and transcriptional activity of HIF-1α in human cervical adenocarcinoma cells. Moreover, the knockdown of PKC-δ inhibited vascular endothelial growth factor expression and angiogenic activity under hypoxia. These effects were completely reversed by PKC-δ overexpression following the knockdown of PKC-δ. Collectively, these findings demonstrate the role of PKC-δ as a new regulator of hypoxia-induced angiogenesis. © 2007 Japanese Cancer Association.