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Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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Related Experiment Video

Updated: Jul 10, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
09:17

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Published on: August 2, 2018

Transgenic models to understand hypoxia-inducible factor function.

Andrew Doedens1, Randall S Johnson

  • 1Molecular Biology Section, Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.

Methods in Enzymology
|November 14, 2007
PubMed
Summary
This summary is machine-generated.

The hypoxia-inducible factor (HIF) pathway regulates cellular responses to low oxygen. Mouse studies reveal essential roles for HIF, VHL, PHD, and VEGF in development and disease.

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Published on: August 12, 2011

Area of Science:

  • Molecular Biology
  • Cellular Physiology
  • Genetics

Background:

  • The hypoxia-inducible factor (HIF) pathway is crucial for mammalian cellular adaptation to low oxygen.
  • HIF controls genes involved in glycolysis and angiogenesis, including vascular endothelial growth factor (VEGF).
  • Regulation involves proteasomal degradation of HIF-alpha subunits, mediated by prolyl-hydroxylase domain (PHD) enzymes and von Hippel-Lindau (VHL) tumor suppressor.

Purpose of the Study:

  • To review insights from murine knockouts and transgenic models of the HIF hypoxia response pathway.
  • To highlight the in vivo effects of manipulating HIF pathway components.

Main Methods:

  • Analysis of murine knockout and transgenic models for HIF, pVHL, PHD, and VEGF.
  • Review of studies examining conditional gene deletion in various tissues.

Main Results:

  • Murine knockouts confirm the essential developmental roles of HIF, pVHL, PHD, and VEGF.
  • Conditional gene manipulation demonstrates profound in vivo effects on physiology, pathology, and tumor biology.

Conclusions:

  • The HIF pathway is vital for development and has significant implications in disease.
  • Murine models are instrumental in understanding the complex roles of HIF pathway components.