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.
journal_name
Methods Enzymoljournal_title
Methods in enzymologyauthors
Doedens A,Johnson RSdoi
10.1016/S0076-6879(07)35005-2subject
Has Abstractpub_date
2007-01-01 00:00:00pages
87-105eissn
0076-6879issn
1557-7988pii
S0076-6879(07)35005-2journal_volume
435pub_type
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