Biochemistry of the hypoxia-inducible factor hydroxylases

From Vessels to Neurons—The Role of Hypoxia Pathway Proteins in Embryonic Neurogenesis

“…Given the critical role of oxygen in cellular metabolism, it is not surprising that organisms have evolved robust oxygen sensing mechanisms that allow them to adapt to changes in oxygen concentration at both systemic and local tissue levels. In vertebrates, cellular oxygen sensing is mediated primarily by the HIF signaling pathway [104][105][106][107][108]. The molecular components of this pathway are expressed in virtually all cells of the body and are remarkably conserved in evolution [107].…”

“…In vertebrates, cellular oxygen sensing is mediated primarily by the HIF signaling pathway [104][105][106][107][108]. The molecular components of this pathway are expressed in virtually all cells of the body and are remarkably conserved in evolution [107]. The key players encompass the heterodimeric hypoxia-inducible factors (HIFs), which are transcription factors belonging to basic helix-loop-helix PAS (Per/Arnt/Sim) protein family [107,109,110] (Figure 2A).…”

“…The molecular components of this pathway are expressed in virtually all cells of the body and are remarkably conserved in evolution [107]. The key players encompass the heterodimeric hypoxia-inducible factors (HIFs), which are transcription factors belonging to basic helix-loop-helix PAS (Per/Arnt/Sim) protein family [107,109,110] (Figure 2A). These heterodimers consist of a constitutively expressed nuclear subunit HIF-1β also known as ARNT (aryl hydrocarbon receptor nuclear translocator) and either the HIF-1α or HIF-2α subunit [104,105,107].…”

“…The key players encompass the heterodimeric hypoxia-inducible factors (HIFs), which are transcription factors belonging to basic helix-loop-helix PAS (Per/Arnt/Sim) protein family [107,109,110] (Figure 2A). These heterodimers consist of a constitutively expressed nuclear subunit HIF-1β also known as ARNT (aryl hydrocarbon receptor nuclear translocator) and either the HIF-1α or HIF-2α subunit [104,105,107]. Both HIF-1α and HIF-2α proteins share a similar domain structure but differ in their expression pattern [107,[111][112][113][114].…”

“…These heterodimers consist of a constitutively expressed nuclear subunit HIF-1β also known as ARNT (aryl hydrocarbon receptor nuclear translocator) and either the HIF-1α or HIF-2α subunit [104,105,107]. Both HIF-1α and HIF-2α proteins share a similar domain structure but differ in their expression pattern [107,[111][112][113][114]. They consist of a N-terminal bHLH (basic helix-loop-helix) domain responsible for DNA binding followed by two PAS dimerization regions, an ODD (oxygen-dependent degradation) domain and Cterminal transactivation domain (TAD) [107,111,112,115].…”