Figure 3

Hypoxia signal transduction. Reduction of cellular O₂ concentration ('down' arrow) is associated with redox changes (Δ) that lead to altered (Δ) phosphorylation of HIF-1α, which increases its stability and transcriptional activity, resulting in the induction of downstream gene expression. Putative inducers (horizontal arrows) and inhibitors (blocked arrows) of different stages in the proposed pathway are indicated. Genistein is an inhibitor of tyrosine protein kinase and competitive inhibitor of ATP in other protein kinase reactions; NaF is a non-specific kinase inhibitor; v-Src is the viral analogue of the mammalian G-coupled protein kinase; MG-132 is a proteasome complex inhibitor.