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
Language
- eng
Conference Location
- United States