Hypoxia-induced factor

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Hypoxia-induced factor 1, α-subunit
Hypoxia-induced factor 1, α-subunit
according to PDB  1H2K

Existing structural data : 1d7g , 1h2k , 1h2l , 1h2m , 1l3e , 1l8c , 1lm8 , 1lq8 , 2ilm , 4ZPR

Properties of human protein
Mass / length primary structure 826 amino acids; 92.7  kDa
Isoforms 2
Identifier
Gene names HIF1A  ; HIF-1alpha; HIF1-ALPHA; MOP1; PASD8
External IDs
Occurrence
Parent taxon Chordates
Orthologue
human mouse
Entrez 3091 15251
Ensemble ENSG00000100644 ENSMUSG00000021109
UniProt Q16665 Q61221
Refseq (mRNA) NM_001530 NM_010431
Refseq (protein) NP_001521 NP_034561
Gene locus Chr 14: 61.23 - 61.28 Mb Chr 12: 75 - 75.05 Mb
PubMed search 3091 15251

Nobel Prize in Physiology / Medicine 2019: Cellular Adaptation Mechanisms to the Availability of Oxygen. With normal cellular availability of oxygen, Hif-1 alpha is hydroxylated on two proline residues and broken down in the proteasome after binding to VHL and ubiquitin. If there is a lack of oxygen, Hif-1 alpha translocates into the cell nucleus, where it binds to HRE as a complex with Hif-1 beta and activates genes that e.g. B. Erythropoiesis, glycolysis and angiogenesis control.

Hypoxia-inducible factors ( HIF ) is a transcription factor , which supply the cell with oxygen regulated by establishing a balance between the oxygen demand and oxygen supply. HIF consists of a labile α-subunit that exists in three isoforms , HIF-1α, HIF-2α and HIF-3α, and a β-subunit.

With normal oxygen supply (normoxia) the α-subunit is hydroxylated on two specific prolyl residues . This hydroxylation leads to HIFα being broken down by the Von Hippel Lindau tumor suppressor protein (pVHL).

When there is insufficient oxygen supply ( hypoxia ), the hydroxylation of HIF-α is inhibited. The thus stabilized transcription factor activates the erythropoietin - gene and a number of other genes which for adapting the cell to a lack of supply of oxygen are required. Furthermore, various experiments indicate HIF-induced expression of growth factors of the group Vascular Endothelial Growth Factor (VEGF).

HIF1a (red) induced by CoCl 2 accumulates in the cell nucleus. Immunofluorescence with mouse endothelial cells

Individual evidence

  1. ↑ KM Mohamed, A. Le u. a .: Correlation between VEGF and HIF-1alpha expression in human oral squamous cell carcinoma. In: Experimental and molecular pathology Volume 76, Number 2, April 2004, pp 143-152. doi : 10.1016 / j.yexmp.2003.10.005 . PMID 15010293 .
  2. ↑ D. Shweiki, A. Itin et al. a .: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. In: Nature Volume 359, Number 6398, October 1992, pp. 843-845. doi : 10.1038 / 359843a0 . PMID 1279431 .

literature

  • Percy, Melanie J. et al .: A Gain-of-Function Mutation in the HIF2A Gene in Familial Erythrocytosis . In: N Engl J Med . No. 358 , 2008, p. 162-168 ( abstract ).
  • Frontiers in Nephrology: Thomas O. Daniel et al .: Integrating Renal Hypoxic Signals in Development and Disease . In: J Am Soc Nephrol . No. 14 , 2003, p. 2693-2694 ( Article ). - Series of overview articles on the fundamentals and medical significance of the oxygen sensor system.

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