Biochemistry of the hypoxia-inducible factor hydroxylases.
Curr Opin Chem Biol
; 79: 102428, 2024 04.
Article
em En
| MEDLINE
| ID: mdl-38330792
ABSTRACT
The hypoxia-inducible factors are α,ß-heterodimeric transcription factors that mediate the chronic response to hypoxia in humans and other animals. Protein hydroxylases belonging to two different structural subfamilies of the Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase superfamily modify HIFα. HIFα prolyl-hydroxylation, as catalysed by the PHDs, regulates HIFα levels and, consequently, α,ß-HIF levels. HIFα asparaginyl-hydroxylation, as catalysed by factor inhibiting HIF (FIH), regulates the transcriptional activity of α,ß-HIF. The activities of the PHDs and FIH are regulated by O2 availability, enabling them to act as hypoxia sensors. We provide an overview of the biochemistry of the HIF hydroxylases, discussing evidence that their kinetic and structural properties may be tuned to their roles in the HIF system. Avenues for future research and therapeutic modulation are discussed.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Oxigenases de Função Mista
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article