The action of HIF-3α variants on HIF-2α-HIF-1β heterodimer formation is directly probed in live cells.

摘要: Hypoxia-inducible factors (HIFs), consisting of α and β subunits, activate various genes to adapt low oxygen environments through their heterodimeric complex formation in the nucleus. While most studies have been extensively focused on HIF-1α isoform, effect HIF-α isoforms between HIF-2α HIF-1β live cells has not reported detail. To probe these interactions a physiological condition, we established fluorescence resonance energy transfer (FRET) assay by introducing fluorescent reporter proteins onto N-termini PC3 cells. After thorough validations our FRET system, showed that both HIF-3α variants likely function as negative regulators heterodimer with We also characterized localization stabilization measured interaction other HIF In contrast previous results showing HIF-3α-mediated blockage translocation, presence did affect HIF-2α, suggesting distinct roles regulation two isoforms.