RGD Reference Report - Hypoxia-inducible factor 2alpha binds to cobalt in vitro. - Rat Genome Database

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Hypoxia-inducible factor 2alpha binds to cobalt in vitro.

Authors: Yuan, Y  Beitner-Johnson, D  Millhorn, DE 
Citation: Yuan Y, etal., Biochem Biophys Res Commun. 2001 Nov 9;288(4):849-54.
RGD ID: 10395380
Pubmed: PMID:11688986   (View Abstract at PubMed)
DOI: DOI:10.1006/bbrc.2001.5835   (Journal Full-text)

The hypoxia-inducible factor (HIF) activates the expression of genes that contain a hypoxia response element (HRE). The alpha subunit of the HIF transcription factors is degraded by proteasome pathways during normoxia, but stabilized under hypoxic conditions. It has previously been established that cobalt causes accumulation of HIF-2alpha and HIF-1alpha. However, little is known about the mechanism by which cobalt mimics hypoxia and stabilizes these transcription factors. We show here that cobalt binds directly to HIF-2alpha in vitro with a high affinity and in an oxygen-dependent manner. We found that HIF-2alpha, which had been stabilized with a proteasome inhibitor, could bind to cobalt, whereas hypoxia-stabilized HIF-2alpha could not. Mutations within the oxygen-dependent degradation domain of HIF-2alpha prevented cobalt binding and led to accumulation of HIF-2alpha during normoxia. This suggests that transition metal such as iron may play a role in regulation of HIF-2alpha in vivo.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cobalt ion binding  IDA 10395380 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Epas1  (endothelial PAS domain protein 1)


Additional Information