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

Nathalie M. Mazure, M. Christiane Brahimi-Horn, Mélanie A. Berta, Emmanuel Benizri, Rebecca L. Bilton, Frédéric Dayan, Amandine Ginouvès, Edurne Berra, Jacques Pouysségur

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)


The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O2 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 O2 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 O2 concentrations.

Original languageEnglish
Pages (from-to)971-980
Number of pages10
JournalBiochemical Pharmacology
Issue number6
Publication statusPublished - 15 Sep 2004
Externally publishedYes


  • ARD1
  • arrest defective-1 protein
  • CBP/p300 interacting transactivator with ED-rich tail 2
  • CITED 2
  • factor inhibiting HIF-1
  • FIH
  • HIF-1
  • hypoxia-inducible factor-1
  • MAPK
  • mitogen-activated protein kinase
  • PHD
  • prolyl hydroxylase domain protein
  • SUMO


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