Disease relevance of HIF1

• Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells [1].

High impact information on HIF1

• Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions [2].
• In vivo, the nuclear Hat1p/Hat2p/Hif1p complex is bound to acetylated histone H4, as well as histone H3 [3].
• Hif1p is also a chromatin assembly factor, promoting the deposition of histones in the presence of a yeast cytosolic extract [3].
• We show that this synergy between IFN and hypoxia is mediated by the direct interaction of the hypoxia inducible factor-1 (HIF-1) and IFN regulatory factor-1 (IRF-1), which are both required for the hypoxic transcription of NOS2 [4].
• The use of this system for the identification and characterization of HIF-1 effectors was first validated by showing that two chemical Hsp90 inhibitors, geldanamycin and radicicol, impaired the activity of HIF-1 in yeast [5].

Biological context of HIF1

• Finally, two ORFs, L1201 and L1205, have weak homology with two yeast hypothetical proteins of unknown function identified by the yeast systematic sequencing genome [6].
• This motif was different from the known hypoxia response elements of S. cerevisiae but showed some similarity to the mammalian HIF-1 binding site [7].

Associations of HIF1 with chemical compounds

• Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that mediates cellular and systemic homeostatic responses to reduce O2 availability, such as erythropoiesis, angiogenesis, and glycolysis [8].
• The activation mechanism of PsADH2 also, in this respect, has similarities to the mammalian HIF-1 system, which is inducible by Co(2+) but not by cyanide [7].

Other interactions of HIF1

• HAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins [9].

Analytical, diagnostic and therapeutic context of HIF1

• In a localization analysis by immunofluorescence microscopy on yeast strains expressing tagged versions of Hat1, Hat2, and Hif1, we have found that all three HAT-B proteins are mainly localized in the nucleus [10].

References