Dioxygenases as O2-dependent regulators of the hypoxic response pathway

Charles E. Dann, Richard K. Bruick

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


A ubiquitous pathway by which mammalian cells sense and respond to changes in oxygen availability relies upon the hypoxic induction of a transcription factor, HIF. HIF in turn activates the expression of an assemblage of genes promoting compensatory shifts in the capacity for anaerobic metabolism, O 2 delivery, and other adaptive processes. The stability and activity of HIF are each regulated as a function of O2. Both mechanisms are directly mediated by posttranslational modification of this transcription factor: hydroxylation of proline and asparagine residues, respectively. These modifications are performed by members of the Fe(II)- and 2-oxoglutarate- dependent dioxygenase family whose activities are directly and indirectly dependent on cellular O2 levels. As such, these oxygenases fill a role as environmental and metabolic sensors, a paradigm that may extend to other biological pathways.

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Dec 9 2005


  • Asparaginyl hydroxylase
  • Dioxygenase
  • FIH-1
  • HIF
  • Hypoxia
  • Oxygen sensing
  • Prolyl hydroxylase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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