Distinguishing to HIF-1α, HIF-2α is unable to compete with MYC for specificity protein 1 (SP1) binding through protein kinase D1 (PKD1)-mediated phosphorylation of HIF-2α.77 In human microvascular endothelial cells, HIF-2 α enhances SP1 activity and also facilitates MYC function to drive IL-8 expression.78 In primary mouse embryo fibroblasts and VHL−/− kidney tumor cells, MYC activity is enhanced by HIF-2α.79,80 Moreover, HIF-2α triggers the activation of MYC by way of the stabilization of the MYC/MAX heterodimer complex under hypoxia. This evidence concerns the gene SP1 and kidney neoplasm.