TY - JOUR
T1 - Protein Kinase C ζ Transactivates Hypoxia-Inducible Factor α by Promoting Its Association with p300 in Renal Cancer
AU - Datta, Kaustubh
AU - Li, Jinping
AU - Bhattacharya, Resham
AU - Gasparian, Levon
AU - Wang, Enfeng
AU - Mukhopadhyay, Debabrata
PY - 2004/1/15
Y1 - 2004/1/15
N2 - Hydroxylation at an asparagine residue at the COOH-terminal activation domain of hypoxia-inducible factor (HIF)-1/2 as is essential for its inactivation under normoxia condition. To date, the mechanism by which HIF-α 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) ζ has an important role in HIF-α activation in RCC. By using dominant negative mutant and small interference RNA approaches, we have demonstrated that the association between HIF-α and p300 is modulated by PKCζ. Moreover, a novel signaling pathway involving phosphatidylinositol 3′-kinase and PKCζ has been shown to be responsible for the activation of HIF-α 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.
AB - Hydroxylation at an asparagine residue at the COOH-terminal activation domain of hypoxia-inducible factor (HIF)-1/2 as is essential for its inactivation under normoxia condition. To date, the mechanism by which HIF-α 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) ζ has an important role in HIF-α activation in RCC. By using dominant negative mutant and small interference RNA approaches, we have demonstrated that the association between HIF-α and p300 is modulated by PKCζ. Moreover, a novel signaling pathway involving phosphatidylinositol 3′-kinase and PKCζ has been shown to be responsible for the activation of HIF-α 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.
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U2 - 10.1158/0008-5472.CAN-03-2706
DO - 10.1158/0008-5472.CAN-03-2706
M3 - Article
C2 - 14744756
AN - SCOPUS:1642556829
SN - 0008-5472
VL - 64
SP - 456
EP - 462
JO - Cancer research
JF - Cancer research
IS - 2
ER -