Details

Autor(en) / Beteiligte

• Percy, Melanie J
• Furlow, Paul W
• Lucas, Guy S
• Li, Xiping
• Lappin, Terence R.J
• McMullin, Mary Frances
• Lee, Frank S

Titel

A Gain-of-Function Mutation in the HIF2A Gene in Familial Erythrocytosis

Ist Teil von

• The New England journal of medicine, 2008-01, Vol.358 (2), p.162-168

Ort / Verlag

Boston, MA: Massachusetts Medical Society

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Hypoxia-inducible factor (HIF) α is a transcription factor that modulates erythropoiesis, angiogenesis, and cellular metabolism. This study of a family with isolated erythrocytosis revealed a mutation in the gene for the HIF-2α isoform, HIF2A, that prevents the hydroxylation of the protein by prolyl hydroxylase–domain protein 2 under normoxic conditions and hence blocks the normal step of degradation by the von Hippel–Lindau protein. This study of a family with isolated erythrocytosis revealed a mutation in the gene for the HIF-2α isoform, HIF2A, that prevents the hydroxylation of the protein by prolyl hydroxylase–domain protein 2 under normoxic conditions and hence blocks the normal step of degradation by the von Hippel–Lindau protein. A widely recognized example of an oxygen-regulated pathway is the erythropoietin system, in which the kidney senses decreased tissue oxygenation and, in turn, produces erythropoietin, thereby increasing the red-cell mass. 1 Studies of the regulation of the EPO gene led to the discovery of HIF, which consists of a labile α subunit and a constitutively expressed β subunit. 2 Under normoxic conditions, the α subunit, which consists of three isoforms — HIF-1α, HIF-2α, and HIF-3α — is hydroxylated on two specific prolyl residues. 3 This hydroxylation targets HIF-α for degradation by the von Hippel–Lindau (VHL) tumor-suppressor protein. 4 Under hypoxic conditions, the hydroxylation is . . .