Protein kinase C zeta transactivates hypoxia-inducible factor alpha by promoting its association with p300 in renal cancer.

Journal Article (Journal Article)

Hydroxylation at an asparagine residue at the COOH-terminal activation domain of hypoxia-inducible factor (HIF)-1/2 alphas is essential for its inactivation under normoxic condition. To date, the mechanism by which HIF-alpha avoids the inhibitory effect of asparagine hydroxylase in renal cell carcinoma (RCC) in normoxia is undefined. We have shown herein that protein kinase C (PKC) zeta has an important role in HIF-alpha activation in RCC. By using dominant negative mutant and small interference RNA approaches, we have demonstrated that the association between HIF-alpha and p300 is modulated by PKCzeta. Moreover, a novel signaling pathway involving phosphatidylinositol 3'-kinase and PKCzeta has been shown to be responsible for the activation of HIF-alpha by inhibiting the mRNA expression of FIH-1 (factor inhibiting HIF-1) in RCC and thereby promoting the transcription of hypoxia-inducible genes such as vascular permeability factor/vascular endothelial growth factor.

Full Text

Duke Authors

Cited Authors

  • Datta, K; Li, J; Bhattacharya, R; Gasparian, L; Wang, E; Mukhopadhyay, D

Published Date

  • January 15, 2004

Published In

Volume / Issue

  • 64 / 2

Start / End Page

  • 456 - 462

PubMed ID

  • 14744756

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-03-2706


  • eng

Conference Location

  • United States