By utilizing a dominant-negative mutant and siRNA approaches, we have demonstrated that the association between HIF a and p300 is modulated by PKC z . Moreover, a novel signaling pathway involving PI-3 kinase and PKC z has been shown to be responsible for the activation of HIF a by inhibiting the mRNA expression of Factor inhibitors for Hypoxia (FIH) in RCC and thereby promoting the transcription of hypoxia inducible genes like VPF/VEGF. Currently, we are trying to understand the minimal promoter region of FIH that is responsible for FIH transcriptional activity in renal cancer.