Figure 1.

Description of the "timer" strategy for HIF imaging in PC3 prostate cancer cells. (A) Under normoxia, hydroxylation of the ODD of HIF-α triggers the degradation of this subunit. Under hypoxia, HIF-α stabilizes, and the dimer HIF-α/HIF-β binds to HRE sequences in the 5xHRE-ODD-luc and 5xHRE-EGFP constructs, resulting in the formation of long-lived EGFP and short-lived ODD-luciferase proteins. (B) Upon reoxygenation, the ODD sequence causes a rapid degradation of the ODD-luciferase fusion protein, whereas EGFP protein levels remain stable for longer periods. The RFP tdTomato is used as a constitutive reporter.