Nur77 upregulates HIF-alpha by inhibiting pVHL-mediated degradation
Experimental & Molecular Medicine
;
: 71-83, 2008.
Article
Dans Anglais
| WPRIM
| ID: wpr-77112
ABSTRACT
In this study, we investigated the role of Nur77, an orphan nuclear receptor, in HIF-alpha transcriptional activity. We found that Nur77 associates and stabilizes HIF-1alpha via indirect interaction. Nur77 was found to interact with pVHL in vivo via the alpha-domain of pVHL. By binding to pVHL, Nur77 competed with elongin C for pVHL binding. Moreover, Nur77-binding to pVHL inhibited the pVHL-mediated ubiquitination of HIF-1alpha and ultimately increased the stability and transcriptional activity of HIF-1alpha. The ligand-binding domain of Nur77 was found to interact with pVHL and the expression of this ligand-binding domain was sufficient to stabilize and transactivate HIF-1alpha. Under the conditions that cobalt chloride was treated or pVHL was knocked down, Nur77 could not stabilize HIF-alpha. Moreover, Nur77 could not further stabilize HIF-2alpha in A498/VHL stable cells, which is consistent with our finding that Nur77 indirectly stabilizes HIF-alpha by binding to pVHL. Thus, our results suggest that an orphan nuclear receptor Nur77 binds to pVHL, thereby stabilizes and increases HIF-alpha transcriptional activity under the non- hypoxic conditions.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Liaison aux protéines
/
Thermodynamique
/
Facteurs de transcription
/
Récepteurs aux stéroïdes
/
Activation de la transcription
/
Régulation positive
/
Maturation post-traductionnelle des protéines
/
Cellules PC12
/
Structure tertiaire des protéines
/
Récepteurs cytoplasmiques et nucléaires
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2008
Type:
Article
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