Entry
Name
HIF-1 signaling pathway - Orcinus orca (killer whale)
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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Organism
Orcinus orca (killer whale) [GN:
oor ]
Gene
101274728 IL6R; interleukin-6 receptor subunit alpha isoform X5 [KO:K05055 ]
101281369 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
101279857 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
101278075 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101278974 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
101283011 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101277568 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101285437 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101281352 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649 ]
101277165 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
101287292 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
101282865 EIF4E; eukaryotic translation initiation factor 4E isoform X4 [KO:K03259 ]
101281614 EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
101272871 VHL; LOW QUALITY PROTEIN: von Hippel-Lindau disease tumor suppressor [KO:K03871 ]
101270436 ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
101281412 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
101269181 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X16 [KO:K04515 ] [EC:2.7.11.17 ]
101287513 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515 ] [EC:2.7.11.17 ]
101281498 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X8 [KO:K04515 ] [EC:2.7.11.17 ]
101271879 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
101278832 LTBR; tumor necrosis factor receptor superfamily member 3 [KO:K03159 ]
101279969 VEGFA; vascular endothelial growth factor A isoform X3 [KO:K05448 ]
101272071 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X2 [KO:K07299 ]
101271748 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1 [KO:K12077 ] [EC:2.7.11.2 ]
101271664 PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
101288495 PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
101287798 PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial isoform X1 [KO:K00162 ] [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 pathway
KO pathway
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