Entry Name HIF-1 signaling pathway - Mus caroli (Ryukyu mouse)
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 Mus caroli (Ryukyu mouse) [GN:
mcal ]
Gene 110284402 Vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
110284502 Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
110286532 Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
110290783 Arnt; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
110290798 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
110290827 Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515 ] [EC:2.7.11.17 ]
110291231 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
110291348 Eif4e; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
110291389 Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
110291421 Il6r; interleukin-6 receptor subunit alpha isoform X1 [KO:K05055 ]
110292183 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110292203 Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
110292210 Eif4e2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
110296136 Vhl; von Hippel-Lindau disease tumor suppressor isoform X2 [KO:K03871 ]
110296619 Ltbr; tumor necrosis factor receptor superfamily member 3 [KO:K03159 ]
110299855 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
110300284 Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
110300336 Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
110301355 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
110305925 Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515 ] [EC:2.7.11.17 ]
110306201 Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
110308009 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110308348 Eif4e1b; eukaryotic translation initiation factor 4E type 1B isoform X1 [KO:K03259 ]
110309790 Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X5 [KO:K04515 ] [EC:2.7.11.17 ]
110312693 Pdk1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077 ] [EC:2.7.11.2 ]
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
