The Function of Hypoxia-Inducible Factor HIF Is Independent of the Endoplasmic Reticulum Protein OS-9Reportar como inadecuado




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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.



Autor: Ulf Brockmeier , Corinna Platzek , Kirsten Schneider, Pauline Patak, André Bernardini, Joachim Fandrey, Eric Metzen

Fuente: http://plos.srce.hr/



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