Figure 1

HIF-1-mediated gene expression in response to hypoxia. Under non-hypoxic conditions, the HIF-1α subunit is subject to ubiquitination and degradation, whereas under hypoxic conditions HIF-1α ubiquitination is inhibited, resulting in the accumulation of HIF-1α, which dimerizes with HIF-1β. The heterodimer recognizes the core binding-site sequence 5'-RCGTG-3' (R, purine) found within the hypoxia response element of a target gene. Once bound, HIF-1 interacts with the transcription initiation complex (consisting of RNA polymerase II and associated factors) via coactivators including CBP, P300, SRC-1, and TIF-2 (see [12] for details and literature citations).