HIF-1: master and commander of the hypoxic world: A pharmacological approach to its regulation by siRNAs

The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O 2 level, which is essential for their viability. It is important that this critical transcription factor be tightly regulated in order for cells to respond to a wide range of O 2 concentrations. HIF-1 regulation by post-translational modification is the central theme of the scenario of O 2 homeostasis. The alpha subunit of HIF-1 is the principal actor while the supporting actors (PHDs, FIH-1, ARD1, CITED2, p300 …) all contribute to the complexity of the grand finale. It is well established that HIF-1 expression and activation correlates with tumor progression and resistance to cancer treatments. We will introduce the different actors involved in HIF-1 regulation, and their mechanisms of action via invalidation by siRNAs and discuss therapies targeting HIF-1, to selectively kill tumor cells that adapt to low O 2 concentrations.