About HIF1A / Hypoxia-Inducible Factor:
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in oxygen levels in the cellular environment, or hypoxia, a medical condition in which the body is deprived of adequate oxygen supply.
HIF1A Mechanism
The alpha subunits of HIF are hydroxylated at conserved proline residues by HIF prolyl-hydroxylases. This allows their recognition and ubiquitination by the VHL E3 ubiquitin ligase, labelling them for rapid degradation by the proteasome. However, this only occurs in normoxic conditions. In comparison, hypoxic conditions cause HIF prolyl-hydroxylase to be inhibited due to using oxygen as a cosubstrate.
Hypoxia-Inducible Factor Structure
The majority of oxygen-breathing species express the highly conserved transcriptional complex HIF-1. HIF-1 is a heterodimer composed of an alpha and a beta subunit. The beta subunit is a constitutively-expressed aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1 belongs to the PER-ARNT-SIM (PAS) subfamily of the basic helix-loop-helix (bHLH) family of transcription factors.
The alpha and beta subunits are similar in structure and both contain the following domains:
●N-terminus: A bHLH domain for DNA binding
●central region: Per-ARNT-Sim (PAS) domain that facilitates heterodimerization
●C-terminus: Recruits transcriptional coregulatory proteins
HIF1A Function
HIF1α expression in haematopoietic stem cells explains the quiescence nature of stem cells for being metabolically maintaining at a low rate. This preserves the potency of stem cells for long periods in a life cycle of an organism.
HIFs are generally vital to development in mammals. If HIF-1 genes are deleted, it results in perinatal death. HIF-1 has also been shown to be vital to chondrocyte survival. This allows the cells to adapt to low-oxygen conditions within the growth plate of bones. Lastly, HIF also plays a central role in regulating the human metabolism