Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis
GL Semenza - Blood, The Journal of the American Society of …, 2022 - ashpublications.org
GL Semenza
Blood, The Journal of the American Society of Hematology, 2022•ashpublications.orgHypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene
transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of
HIFs on proline and asparagine residues regulates protein stability and transcriptional
activity, respectively. Mutations in genes encoding components of the O2-sensing pathway
cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases
are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in …
transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of
HIFs on proline and asparagine residues regulates protein stability and transcriptional
activity, respectively. Mutations in genes encoding components of the O2-sensing pathway
cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases
are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in …
Abstract
Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcriptional activity, respectively. Mutations in genes encoding components of the O2-sensing pathway cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcomes in these disorders.
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