From erythropoietin to oxygen: Hypoxia-inducible factor hydroxylases and the hypoxia signal pathway

The regulation of blood red cell production by the hormone erythropoietin (Epo) provides a paradigm for control of gene expression by oxygen. Analysis of this pathway has revealed a widespread system of gene regulation based on a transcriptional complex termed hypoxia-inducible factor (HIF). Hydroxylation of specific prolyl and asparinyl residues in the a subunit of HIF by a series of non-haem iron-dependent dioxygenases has been defined as a novel mechanism of protein modification that transduces the oxygen-sensitive signal. Copyright (C) 2002 S. Karger AG, Basel.