ARNT-interacting protein, Basic-helix-loop-helix-PAS protein MOP1, Class E basic helix-loop-helix protein 78 (bHLHe78), Hypoxia inducible factor 1 alpha, Member of PAS superfamily 1 (MOP1), PAS domain-containing protein 8 (PASD8)
HIF1 (hypoxia-inducible factor 1), a heterodimeric transcription factor complex central to cellular response to hypoxia, consists of two subunits (HIF-1 alpha and HIF-1 beta) which are basic helix-loop-helix proteins of the PAS (Per, ARNT, Sim) family. Expression of HIF-1 alpha protein is regulated by cellular oxygen level alterations as well as in oxygen-independent manner via different cytokines (throµgh the PI3K-AKT-mTOR pathway), growth factors, oncogenic activation, or loss of tumor suppressor function etc. In normoxic cells, HIF-1 alpha is proline hydroxylated leading to a conformational change that promotes its binding to the VLH (von Hippel Lindau) protein E3 ligase complex, ubiquitination and followed by rapid proteasomal degradation. Hypoxia as well as chemical hydroxylase inhibitors (desferrioxamine, cobalt etc.) inhibit HIF-1 alpha degradation and lead to its accumulation in the cells, whereas, contrastingly, HIF-1 beta/ARNT (AhR nuclear translocator) remains stable under both conditions. Besides their critical role in hypoxic response, HIF1s regulates the transcription of genes responsible for angiogenesis, erythropoiesis/iron-metabolism, glucose metabolism, cell proliferation/survival, adipogenesis, carotid body formation, B lymphocyte development and immune reactions.
