Dioxygenases as O2-dependent regulators of the hypoxic response pathway

Charles E. Dann, Richard K. Bruick

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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
Volume338
Issue number1
DOIs
StatePublished - Dec 9 2005

Fingerprint

Dioxygenases
Transcription Factors
Anaerobiosis
Oxygenases
Hydroxylation
Asparagine
Post Translational Protein Processing
Proline
Metabolism
Genes
Cells
Availability
Oxygen
Gene Expression
Sensors
alpha-ketoglutaric acid

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Dioxygenases as O2-dependent regulators of the hypoxic response pathway. / Dann, Charles E.; Bruick, Richard K.

In: Biochemical and Biophysical Research Communications, Vol. 338, No. 1, 09.12.2005, p. 639-647.

Research output: Contribution to journalArticle

Dann, Charles E. ; Bruick, Richard K. / Dioxygenases as O2-dependent regulators of the hypoxic response pathway. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 338, No. 1. pp. 639-647.
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