Entry Name HIF-1 signaling pathway - Pteropus alecto (black flying fox)
Description Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a constitutively-expressed HIF-1beta subunit. Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxia, HIF-1 alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors.
Class Environmental Information Processing; Signal transductionBRITE hierarchy
Pathway map Organism Pteropus alecto (black flying fox) [GN:
pale ]
Gene 102879163 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
102879453 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102880320 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102880692 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
102881655 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
102882467 PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
102883688 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1 [KO:K12077 ] [EC:2.7.11.2 ]
102884374 STAT3; LOW QUALITY PROTEIN: signal transducer and activator of transcription 3 [KO:K04692 ]
102885620 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
102885691 ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
102886421 LTBR; tumor necrosis factor receptor superfamily member 3 isoform X3 [KO:K03159 ]
102888385 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
102889227 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
102889576 PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102890394 VEGFA; vascular endothelial growth factor A isoform X2 [KO:K05448 ]
102894133 EPAS1; endothelial PAS domain-containing protein 1 isoform X1 [KO:K09095 ]
102894970 EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259 ]
102896228 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
102897181 PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
102898723 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Semenza GL
Title Oxygen homeostasis.
Journal Reference Authors Mole DR, Ratcliffe PJ
Title Cellular oxygen sensing in health and disease.
Journal Reference Authors Kaelin WG Jr, Ratcliffe PJ
Title Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Journal Reference Authors Palazon A, Aragones J, Morales-Kastresana A, de Landazuri MO, Melero I
Title Molecular pathways: hypoxia response in immune cells fighting or promoting cancer.
Journal Reference Authors Majmundar AJ, Wong WJ, Simon MC
Title Hypoxia-inducible factors and the response to hypoxic stress.
Journal Reference Authors Greer SN, Metcalf JL, Wang Y, Ohh M
Title The updated biology of hypoxia-inducible factor.
Journal Reference Authors Zagorska A, Dulak J
Title HIF-1: the knowns and unknowns of hypoxia sensing.
Journal Acta Biochim Pol 51:563-85 (2004)
Reference Authors Semenza GL
Title Regulation of oxygen homeostasis by hypoxia-inducible factor 1.
Journal Reference Authors Wenger RH, Stiehl DP, Camenisch G
Title Integration of oxygen signaling at the consensus HRE.
Journal Reference Authors Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW
Title Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions.
Journal Reference Authors Weidemann A, Johnson RS
Title Biology of HIF-1alpha.
Journal Reference Authors Harris AL
Title Hypoxia--a key regulatory factor in tumour growth.
Journal Reference Authors Knaup KX, Jozefowski K, Schmidt R, Bernhardt WM, Weidemann A, Juergensen JS, Warnecke C, Eckardt KU, Wiesener MS
Title Mutual regulation of hypoxia-inducible factor and mammalian target of rapamycin as a function of oxygen availability.
Journal Reference Authors Kaluz S, Kaluzova M, Stanbridge EJ
Title Regulation of gene expression by hypoxia: integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element.
Journal Reference Authors Cadenas S, Aragones J, Landazuri MO
Title Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease.
Journal Reference Authors Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J
Title Oxygen-sensing under the influence of nitric oxide.
Journal Related KO pathway
