Protein kinase C-delta regulates the stability of hypoxia-inducible factor-1 alpha under hypoxia.
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-delta (PKC-delta) is activated by hypoxia, increases the protein stability and transcriptional activity of HIF-1alpha in human cervical adenocarcinoma cells. Moreover, the knockdown of PKC-delta inhibited vascular endothelial growth factor expression and angiogenic activity under hypoxia. These effects were completely reversed by PKC-delta overexpression following the knockdown of PKC-delta. Collectively, these findings demonstrate the role of PKC-delta as a new regulator of hypoxia-induced angiogenesis.
Lee
Ji-Won
JW
Neurovascular Coordination Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Park
Jeong Ae
JA
Kim
Se-Hee
SH
Seo
Ji Hae
JH
Lim
Kyung-Joon
KJ
Jeong
Joo-Won
JW
Jeong
Chul-Ho
CH
Chun
Kwang-Hoon
KH
Lee
Seung-Ki
SK
Kwon
Young-Guen
YG
Kim
Kyu-Won
KW
D002460:Cell Line; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051745:Protein Kinase C-delta / Q000502:physiology*; D015533:Transcriptional Activation
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051745:Protein Kinase C-delta