Hypoxia Signaling 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
mTORAMRe14217mTOR (1L6) Rabbit Monoclonal AntibodyHuman,Mouse,Rat,Chicken,Bovine,PigWB,IHC,IF,IP,ELISA
NF-κBAMRe02341NF-KB p100 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,IP
NF-κBAMRe04521NF-KB p65 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,IP
HIF-1 alphaAMRe05346HIF-1 alpha Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
HIF-2 alphaAMRe06783HIF-2 alpha Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
Caspase-1AMRe07956Caspase-1 (16E17) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IP
PI3KAMRe08001PI3K p85 alpha Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
AKT1AMRe08007AKT1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
AKT2AMRe08008AKT2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
AKT3AMRe08009AKT3 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
PDK1AMRe08010PDK1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
PTENAMRe08011PTEN Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
TSC1AMRe08012TSC1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
TSC2AMRe08013TSC2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
RHEBAMRe08014RHEB Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
RAPTORAMRe08015RAPTOR Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
RAPamycinAMRe08016RAPamycin Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
p70 S6 KinaseAMRe08017p70 S6 Kinase Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
4E-BP1AMRe080184E-BP1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
eIF4EAMRe08019eIF4E Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
PHD1AMRe08021PHD1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
PHD2AMRe08022PHD2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
PHD3AMRe08023PHD3 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
VHLAMRe08024VHL Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
p300AMRe08025p300 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
CBPAMRe08026CBP Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
HDAC1AMRe08027HDAC1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
HDAC2AMRe08028HDAC2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP
HDAC3AMRe08029HDAC3 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC/IF,IP

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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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