Entry
Name
HIF-1 signaling pathway - Macaca mulatta (rhesus 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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Organism
Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene
716690 IL6R; interleukin-6 receptor subunit alpha isoform X2 [KO:K05055 ]
574128 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
715919 RELA; transcription factor p65 isoform X1 [KO:K04735 ]
710324 NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
698619 EGF; pro-epidermal growth factor isoform X2 [KO:K04357 ]
698444 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
721821 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369 ] [EC:2.7.12.2 ]
710061 MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X3 [KO:K04372 ] [EC:2.7.11.1 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
703628 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
713487 EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259 ]
706751 EIF4E; eukaryotic translation initiation factor 4E [KO:K03259 ]
703732 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
704678 HIF1A; hypoxia-inducible factor 1-alpha isoform X4 [KO:K08268 ]
106996285 VHL; von Hippel-Lindau disease tumor suppressor isoform X1 [KO:K03871 ]
698922 ELOC; transcription elongation factor B polypeptide 1 [KO:K03872 ]
715971 ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
696542 CYBB; cytochrome b-245 heavy chain [KO:K21421 ] [EC:1.-.-.-]
697069 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
714173 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
705980 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515 ] [EC:2.7.11.17 ]
702504 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
706977 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X11 [KO:K04515 ] [EC:2.7.11.17 ]
710540 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
574348 TIMP1; metalloproteinase inhibitor 1 precursor [KO:K16451 ]
712550 LTBR; tumor necrosis factor receptor superfamily member 3 precursor [KO:K03159 ]
574209 VEGFA; vascular endothelial growth factor A isoform 1 precursor [KO:K05448 ]
713883 SERPINE1; plasminogen activator inhibitor 1 [KO:K03982 ]
698931 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
697772 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077 ] [EC:2.7.11.2 ]
722330 PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850 ] [EC:2.7.1.11 ]
719199 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
697188 CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
709359 PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
100423990 PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
574227 PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [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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