| Autor: |
van Wijk R; Laboratory for Red Blood Cell Research, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands., Sutherland S, Van Wesel AC, Huizinga EG, Percy MJ, Bierings M, Lee FS |
| Jazyk: |
angličtina |
| Zdroj: |
Haematologica [Haematologica] 2010 May; Vol. 95 (5), pp. 829-32. Date of Electronic Publication: 2009 Dec 08. |
| DOI: |
10.3324/haematol.2009.017582 |
| Abstrakt: |
The ERYTHROPOIETIN (EPO) gene is regulated by the transcription factor Hypoxia Inducible Factor-alpha (HIF-alpha). In this pathway, Prolyl Hydroxylase Domain protein 2 (PHD2) hydroxylates two prolyl residues in HIF-alpha, which in turn promotes HIF-alpha degradation by the von Hippel Lindau (VHL) protein. Evidence that HIF-2alpha is the important isoform for EPO regulation in humans comes from the recent observation that mutations in the HIF2A gene are associated with cases of erythrocytosis. We report here a new erythrocytosis-associated mutation, p.Asp539Glu, in the HIF2A gene. Similar to all reported cases, the affected residue is in close vicinity and C-terminal to the primary hydroxylation site in HIF-2alpha, Pro531. This mutation, however, is notable in producing a rather subtle amino acid substitution. Nonetheless, we find that this mutation compromises binding of HIF-2alpha to both PHD2 and VHL, and we propose that this mutation is the cause of erythrocytosis in this individual. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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