ABSTRACT
The erythropoietin(EPO) system was used to study the molecular mechanisms associated with the induction of hypoxia responsive genes and from these investigations the hypoxia-inducible factors (HIFs) was identified as a key transcriptional hypoxic regulator of EPO. Subsequent research has now found that a large number of other hypoxia-inducible genes are also induced by HIF under hypoxic conditions. The HIF transcriptional complex is a heterodimer consisting of an alpha subunit and a beta subunit. Recently, two oxygen sensor, oxygen-dependent prolyl and asparaginyl hydroxylation were found,and it is the first time that the oxygen sensor had been described for higher organisms. This review focused on the structure and functions of HIF and the regulation of HIF proteins by hypoxia and oxygen sensors.