A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation


Autoria(s): Percy, Melanie J; Mooney, Sharon M; McMullin, Mary Frances; Flores, Adrian; Lappin, Terence R J; Lee, Frank S
Data(s)

09/09/2003

Resumo

The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).

Identificador

http://pure.qub.ac.uk/portal/en/publications/a-common-polymorphism-in-the-oxygendependent-degradation-odd-domain-of-hypoxia-inducible-factor1alpha-hif1alpha-does-not-impair-pro564-hydroxylation(33113eab-98ae-4522-87b4-600cc3f7fc03).html

http://dx.doi.org/10.1186/1476-4598-2-31

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Percy , M J , Mooney , S M , McMullin , M F , Flores , A , Lappin , T R J & Lee , F S 2003 , ' A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation ' Molecular Cancer Therapeutics , vol 2 , pp. 31-31 . DOI: 10.1186/1476-4598-2-31

Palavras-Chave #Binding Sites #DNA #DNA Mutational Analysis #Female #Humans #Hydroxylation #Hypoxia-Inducible Factor 1, alpha Subunit #Male #Mutation, Missense #Oxygen #Polycythemia #Polymorphism, Genetic #Proline #Transcription Factors
Tipo

article