Brockmeier, Ulf; Platzek, Corinna; Schneider, Kirsten; Patak, Pauline; Bernardini, André; Fandrey, Joachim; Metzen, Eric:
The Function of Hypoxia-Inducible Factor (HIF) Is Independent of the Endoplasmic Reticulum Protein OS-9
In: PLoS ONE, Jg. 6 (2011), Heft 4, S. e19151
2011Artikel/Aufsatz in ZeitschriftOA Gold
MedizinMedizinische Fakultät » Universitätsklinikum Essen » Institut für PhysiologieMedizinische Fakultät » Universitätsklinikum Essen » Klinik für NeurologieForschungszentren » Zentrum für Medizinische Biotechnologie (ZMB)
Damit verbunden: 1 Publikation(en)
Titel in Englisch:
The Function of Hypoxia-Inducible Factor (HIF) Is Independent of the Endoplasmic Reticulum Protein OS-9
Autor*in:
Brockmeier, Ulf;Platzek, Corinna;Schneider, Kirsten;Patak, Pauline;Bernardini, André;Fandrey, JoachimUDE
GND
1146603150
LSF ID
11807
ORCID
0000-0001-9585-0531ORCID iD
Sonstiges
der Hochschule zugeordnete*r Autor*in
;
Metzen, EricUDE
LSF ID
50408
ORCID
0000-0002-2740-3219ORCID iD
Sonstiges
der Hochschule zugeordnete*r Autor*in
Erscheinungsjahr:
2011
Open Access?:
OA Gold
DuEPublico 1 ID
EVALuna Biblio ID
19332
Web of Science ID
PubMed ID
Notiz:
OA Förderung 2011
Sprache des Textes:
Englisch

Abstract in Englisch:

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.