Ang, SO and Chen, H and Hirota, K and Gordeuk, VR and Jelinek, J and Guan, YL and Liu, EL and Sergueeva, AI and Miasnikova, GY and Mole, D and Maxwell, PH and Stockton, DW and Semenza, GL and Prchal, JT (2002) Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. NAT GENET , 32 (4) 614 - 621. 10.1038/ng1019.
Full text not available from this repository.
Chuvash polycythemia is an autosomal recessive disorder that is endemic to the mid-Volga River region. We previously mapped the locus associated with Chuvash polycythemia to chromosome 3p25. The gene associated with von Hippel-Lindau syndrome, VHL, maps to this region, and homozygosity with respect to a C-->T missense mutation in VHL, causing an arginine-to-tryptophan change at amino-acid residue 200 (Arg200Trp), was identified in all individuals affected with Chuvash polycythemia. The protein VHL modulates the ubiquitination and subsequent destruction of hypoxia-inducible factor 1, subunit alpha(HIF1alpha). Our data indicate that the Arg200Trp substitution impairs the interaction of VHL with HIF1alpha reducing the rate of degradation of HIF1alpha and resulting in increased expression of downstream target genes including EPO (encoding erythropoietin), SLC2A1 (also known as GLUT1, encoding solute carrier family 2 (facilitated glucose transporter), member 1), TF (encoding transferrin), TFRC (encoding transferrin receptor (p90, CD71)) and VEGF (encoding vascular endothelial growth factor).
|Title:||Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia|
|Keywords:||TUMOR-SUPPRESSOR PROTEIN, INDUCIBLE FACTOR 1-ALPHA, HIPPEL-LINDAU-DISEASE, TRANSCRIPTIONAL ACTIVITY, PROLYL HYDROXYLATION/, HIF-ALPHA, VHL GENE, HYPOXIA, ERYTHROPOIESIS, ERYTHROCYTOSIS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
Archive Staff Only: edit this record