HIF-1alpha Upregulation due to Depletion of the Free Ubiquitin Pool
Journal of Korean Medical Science
;
: 1388-1395, 2015.
Artículo
en Inglés
| WPRIM
| ID: wpr-183083
ABSTRACT
Hypoxia-inducible factor 1alpha (HIF-1alpha), which transactivates a variety of hypoxia-induced genes, is rapidly degraded under nomoxia through the hydroxylation-ubiquitination-proteasome pathway. In this study, we addressed how HIF-1alpha is stabilized by proteasome inhibitors. The ubiquitin pool was rapidly reduced after proteasome inhibition, followed by the accumulation of non-ubiquitinated HIF-1alpha. The poly-ubiquitination of HIF-1alpha was resumed by restoration of free ubiquitin, which suggests that the HIF-1alpha stabilization under proteasome inhibition is attributed to depletion of the free ubiquitin pool. Ni2+ and Zn2+ also stabilized HIF-1alpha with depletion of the free ubiquitin pool and these effects of metal ions were attenuated by restoration of free ubiquitin. Ni2+ and Zn2+ may disturb the recycling of free ubiquitin, as MG132 does. Based on these results, the state of the ubiquitin pool seems to be another critical factor determining the cellular level of HIF-1alpha.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Zinc
/
Hipoxia de la Célula
/
Regulación hacia Arriba
/
Ubiquitina
/
Línea Celular Tumoral
/
Células HCT116
/
Complejo de la Endopetidasa Proteasomal
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Ubiquitinación
/
Células HEK293
Límite:
Humanos
Idioma:
Inglés
Revista:
Journal of Korean Medical Science
Año:
2015
Tipo del documento:
Artículo
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