Entry
Name
HIF-1 signaling pathway - Manis javanica (Malayan pangolin)
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
Manis javanica (Malayan pangolin) [GN:
mjv ]
Gene
108393946 IL6R; interleukin-6 receptor subunit alpha isoform X2 [KO:K05055 ]
108386068 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
108406544 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
108390365 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
108400388 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
108383561 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
108390475 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
108395975 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
108409141 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
108408568 EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
108383725 EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X3 [KO:K03259 ]
108388478 eukaryotic translation initiation factor 4E type 1B-like [KO:K03259 ]
108402196 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
108408262 ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
108400464 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
108385398 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
108394027 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
108398760 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
108400883 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
108387605 LTBR; tumor necrosis factor receptor superfamily member 3 isoform X1 [KO:K03159 ]
108406715 SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299 ]
108391482 PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1 [KO:K12077 ] [EC:2.7.11.2 ]
108400925 PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
108401242 PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
108404130 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161 ] [EC:1.2.4.1 ]
108394911 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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