Entry Name HIF-1 signaling pathway - Rhinopithecus roxellana (golden snub-nosed monkey)
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 Rhinopithecus roxellana (golden snub-nosed monkey) [GN:
rro ]
Gene 104655162 EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
104662124 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
104662315 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
104663050 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
104663493 IL6R; interleukin-6 receptor subunit alpha isoform X1 [KO:K05055 ]
104665061 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
104667362 VEGFA; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
104668343 CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624 ]
104669015 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
104669984 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
104670410 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
104670605 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
104671146 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
104672220 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
104673517 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077 ] [EC:2.7.11.2 ]
104675620 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
104676623 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
104679650 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
104679850 PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
104680124 LTBR; tumor necrosis factor receptor superfamily member 3 isoform X1 [KO:K03159 ]
104680286 STAT3; signal transducer and activator of transcription 3 isoform X3 [KO:K04692 ]
104680439 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
104680672 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
104681067 ARNT; LOW QUALITY PROTEIN: aryl hydrocarbon receptor nuclear translocator [KO:K09097 ]
104682411 PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
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
