STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination
Experimental & Molecular Medicine
;
: 479-485, 2008.
Article
Dans Anglais
| WPRIM
| ID: wpr-84655
ABSTRACT
Hypoxia-inducible factor 1alpha (HIF-1alpha) is rapidly degraded by the ubiquitin-proteasome pathway under normoxic conditions. Ubiquitination of HIF-1alpha is mediated by interaction with von Hippel-Lindau tumor suppressor protein (pVHL). In our previous report, we found that hypoxia-induced active signal transducer and activator of transcription3 (STAT3) accelerated the accumulation of HIF-1alpha protein and prolonged its half-life in solid tumor cells. However, its specific mechanisms are not fully understood. Thus, we examined the role of STAT3 in the mechanism of pVHL-mediated HIF-1alpha stability. We found that STAT3 interacts with C-terminal domain of HIF-1alpha and stabilizes HIF-1alpha by inhibition of pVHL binding to HIF-1alpha. The binding between HIF-1alpha and pVHL, negative regulator of HIF-1alpha stability, was interfered dose-dependently by overexpressed constitutive active STAT3. Moreover, we found that the enhanced HIF-1alpha protein levels by active STAT3 are due to decrease of poly-ubiquitination of HIF-1alpha protein via inhibition of interaction between pVHL and HIF-1alpha. Taken together, our results suggest that STAT3 decreases the pVHL-mediated ubiquitination of HIF-1alpha through competition with pVHL for binding to HIF-1alpha, and then stabilizes HIF-1alpha protein levels.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Liaison aux protéines
/
Transfection
/
Immunotransfert
/
Transduction du signal
/
Chlorocebus aethiops
/
Cellules COS
/
Lignée cellulaire tumorale
/
Immunoprécipitation
/
Protéine Von Hippel-Lindau supresseur de tumeur
/
Facteur de transcription STAT-3
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2008
Type:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS