HIF1 alpha

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 (through 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.

[hypoxia-inducible factor 1-alpha isoform 3; Hypoxia-inducible factor 1-alpha; hypoxia-inducible factor 1-alpha; HIF-1-alpha; member of PAS protein 1; ARNT interacting protein; ARNT-interacting protein; member of PAS superfamily 1; hypoxia-inducible factor1alpha; PAS domain-containing protein 8; basic-helix-loop-helix-PAS protein MOP1; class E basic helix-loop-helix protein 78; hypoxia-inducible factor 1 alpha isoform I.3; hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; Class E basic helix-loop-helix protein 78; bHLHe78; Member of PAS protein 1; PAS domain-containing protein 8]