Conditional inactivation of HIF-1 using intrabodies.
Cell Oncol
; 30(5): 397-409, 2008.
Article
en En
| MEDLINE
| ID: mdl-18791271
ABSTRACT
Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here we provide a novel approach for HIF-1 targeted therapy using single-domain llama antibodies directed against the HIF-1alpha oxygen dependent degradation domain which encompass the N-terminal transactivation domain. Conditional expression of HIF intrabodies in mammalian cells interfered with binding to pVHL and inhibited hypoxia induced activation of endogenous target genes. Inducible intrabody targeting is a highly specific strategy for temporal protein inactivation and may have applications for disease treatment.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Inmunoglobulinas
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Especificidad de Anticuerpos
Límite:
Animals
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Humans
Idioma:
En
Año:
2008
Tipo del documento:
Article