Hypoxia Pathway

Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor that plays a critical role in the cellular response to hypoxia. The HIF1 complex consists of two subunits, HIF-1α and HIF-1β, which are basic helix-loop-helix proteins of the PAS (Per, ARNT, Sim) family. HIF1 regulates the transcription of a broad range of genes that facilitate responses to the hypoxic environment, including genes regulating angiogenesis, erythropoiesis, cell cycle, metabolism, and apoptosis. The widely expressed HIF-1α is typically degraded rapidly in normoxic cells by the ubiquitin/proteasomal pathway. Under normoxic conditions, HIF-1α is proline hydroxylated leading to a conformational change that promotes binding to the von Hippel-Lindau protein (VHL) E3 ligase complex; ubiquitination and proteasomal degradation follows. Both hypoxic conditions and chemical hydroxylase inhibitors (such as desferrioxamine and cobalt) inhibit HIF-1α degradation and lead to its stabilization. In addition, HIF-1α can be induced in an oxygen-independent manner by various cytokines through the PI3K-AKT-mTOR pathway.

Product List

TargetCatalog#Product NameReactivityApplication


HIF-1 alpha (3M10)


AMRe12017


HIF-1 alpha (3M10) Rabbit Monoclonal Antibody

Human

WB,IHC-P,ICC/IF,FC,IP,IF-P

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References

  • HIF1 and oxygen sensing in the brain. Sharp FR, et al. Nat Rev Neurosci. 2004. [PMID: 15152194]
  • Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Wang GL, et al. Proc Natl Acad Sci U S A. 1995 . [PMID: 7539918]
  • Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Jaakkola P, et al. Science. 2001. [PMID: 11292861]
  • The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Maxwell PH, et al. Nature. 1999. [PMID: 10353251]
  • Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. Fukuda R, et al. J Biol Chem. 2002. [PMID: 12149254]
  • Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Jiang BH, et al. Cell Growth Differ. 2001. [PMID: 11457733]
  • HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Laughner E, et al. Mol Cell Biol. 2001. [PMID: 11359907]
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