The function of hypoxia-inducible factor (HIF) is independent of the endoplasmic reticulum protein OS-9.

The protein "amplified in osteosarcoma-9" (OS-9) has been shown previously to interact with the prolyl hydroxylases PHD2 and PHD3. These enzymes initiate oxygen-dependent degradation of the α-subunit of hypoxia-inducible factor (HIF), a transcription factor that adapts cells to insufficient oxygen supply (hypoxia). A new model has been proposed where OS-9 ...
triggers PHD dependent degradation of HIF-α. It was the aim of our study to define the molecular mode of action of OS-9 in the regulation of PHD and HIF activity. Although initial co-immunoprecipitation experiments confirmed physical interaction between OS-9 and PHD2, neither overexpression nor lentiviral inhibition of OS-9 expression affected HIF regulation. Subcellular localization experiments revealed a distinct reticular staining pattern for OS-9 while PHD2 was mainly localized in the cytoplasm. Further cell fractionation experiments and glycosylation tests indicated that OS-9 is a luminal ER protein. In vivo protein interaction analysis by fluorescence resonance energy transfer (FRET) showed no significant physical interaction of overexpressed PHD2-CFP and OS-9-YFP. We conclude that OS-9 plays no direct functional role in HIF degradation since physical interaction of OS-9 with oxygen sensing HIF prolyl hydroxylases cannot occur in vivo due to their different subcellular localization.
Mesh Terms:
Anoxia, Antibodies, Monoclonal, Cell Line, Tumor, Cytoplasm, Endoplasmic Reticulum, Fibroblasts, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Glycosylation, HeLa Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Lectins, Models, Biological, Neoplasm Proteins, Oxygen, Protein Structure, Tertiary
PLoS ONE
Date: May. 12, 2011
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