Transgenic models to understand hypoxia-inducible factor function.
Methods Enzymol
; 435: 87-105, 2007.
Article
em En
| MEDLINE
| ID: mdl-17998050
ABSTRACT
The hypoxia-inducible factor (HIF) is a heterodimeric basic helix-loop-helix (bHLH) transcription factor that controls the mammalian cellular transcriptional response to low oxygen tension by up-regulating genes including glycolytic enzymes and angiogenic factors, such as the vascular endothelial growth factor (VEGF). Under normal oxygen tensions, the pathway is negatively regulated by posttranslational proteasomal degradation of HIF-alpha (alpha) subunits in a pathway requiring prolyl-hydroxylase domain (PHD) containing enzyme modification followed by von-Hippel Lindau (VHL) tumor suppressor polyubiquitination (pVHL). Murine knockouts of HIF, pVHL, PHD, and VEGF have demonstrated the essential role of these hypoxic response pathway proteins in development. Conditional deletion of these genes in a wide range of tissues has further shown that ablation or overexpression of the pathway has profound in vivo effects, with important implications for physiology, pathology, and tumor biology. This review aims to summarize the insights garnered from key murine knockouts and transgenics involving components of the HIF hypoxia response pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Crescimento e Desenvolvimento
/
Fator 1 Induzível por Hipóxia
/
Modelos Biológicos
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Methods Enzymol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos