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 language | English (US) |
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Pages (from-to) | 639-647 |
Number of pages | 9 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 338 |
Issue number | 1 |
DOIs | |
State | Published - Dec 9 2005 |
Keywords
- Asparaginyl hydroxylase
- Dioxygenase
- FIH-1
- HIF
- Hypoxia
- Oxygen sensing
- Prolyl hydroxylase
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology