HIF αpathway - Abcam
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Discover more at abcam.com Transcription of Target Genes: Angiogenesis: • Vascular endothelial growth factor • Endothelial growth factor Metabolism: • Glucose transporter-1 • Hexokinase 2 • Glyceraldehyde-3 phosphate dehydrogenase • Enolase-1 Vascular function: • Inducible nitric oxide synthase • Endothelial nitric oxide synthase • Endothelin-1 Cell migration: • C-X-C chemokine receptor type 4 (CXCR-4) Erythropoiesis: • Erythropoietin Transcription of Target Genes Under normoxic conditions HIFα is hydroxylated by HIFα -specific prolyl hydroxylases (PHD1-3), which are oxygen sensing. Hydroxylation triggers poly-ubiquitylation of HIFα and targets it for proteasomal degradation by an E3 ubiquitin ligase, the von Hippel-Lindau protein (pVHL) complex. Hypoxia and TCA cycle intermediates inhibit hydroxylation and stabilize the protein. HIFα subunits are also substrates for an asparaginyl hydroxylase factor-inhibiting HIF1α (FIH1). This enzyme is also oxygen sensing and hydroxylation by FIH1 disrupts a critical interaction between HIFα subunits and co-activators such as p300/CBP, impairing HIF transcriptional activity. Regulation of HIFα stability can also be mediated by an oxygen-independent pathway. In the cytoplasm, HIFα is bound to heat-shock protein 90 (Hsp90) and this association leads to enhanced stability of the subunit. However, upon displacement of Hsp90 by Hsp90 inhibitors, receptor of activated protein C kinase (RACK1) is able to bind and acts to recruit ubiquitin ligase machinery and potentiate the degradation of the α-subunit. Co-factors: • Alpha-Ketoglutarate • Fe 2+ • Ascorbic acid • Oxygen Transcriptional co-activators: • p300 • CBP - Creb binding protein • SRC-1 - Steroid receptor co-activator 1 • TIF-2 - Transcription intermediary factor 2 • Ref-1 - Redox factor 1 Produced in collaboration with Claudie Hooper, King’s College London HIFα pathway
Transcript of HIF αpathway - Abcam
Discover more at abcam.com
Transcription of Target Genes:
Angiogenesis:• Vascular endothelial growth factor• Endothelial growth factorMetabolism:• Glucose transporter-1• Hexokinase 2• Glyceraldehyde-3 phosphate dehydrogenase• Enolase-1Vascular function:• Inducible nitric oxide synthase• Endothelial nitric oxide synthase• Endothelin-1Cell migration:• C-X-C chemokine receptor type 4 (CXCR-4)Erythropoiesis:• Erythropoietin
Transcription of Target Genes
Under normoxic conditions HIFα is hydroxylated by HIFα -specific prolylhydroxylases (PHD1-3), which are oxygen sensing. Hydroxylation triggerspoly-ubiquitylation of HIFα and targets it for proteasomal degradation by anE3 ubiquitin ligase, the von Hippel-Lindau protein (pVHL) complex. Hypoxiaand TCA cycle intermediates inhibit hydroxylation and stabilize the protein.HIFα subunits are also substrates for an asparaginyl hydroxylasefactor-inhibiting HIF1α (FIH1). This enzyme is also oxygen sensing andhydroxylation by FIH1 disrupts a critical interaction between HIFα subunitsand co-activators such as p300/CBP, impairing HIF transcriptional activity.
Regulation of HIFα stability can also be mediated by an oxygen-independentpathway. In the cytoplasm, HIFα is bound to heat-shock protein 90 (Hsp90)and this association leads to enhanced stability of the subunit. However,upon displacement of Hsp90 by Hsp90 inhibitors, receptor of activatedprotein C kinase (RACK1) is able to bind and acts to recruit ubiquitin ligasemachinery and potentiate the degradation of the α-subunit.
Co-factors:
• Alpha-Ketoglutarate• Fe2+• Ascorbic acid• Oxygen
Transcriptional co-activators:
• p300• CBP - Creb binding protein• SRC-1 - Steroid receptor co-activator 1• TIF-2 - Transcription intermediary factor 2• Ref-1 - Redox factor 1
Produced in collaboration with Claudie Hooper, King’s College London
HIFα pathway
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Featured antibodies
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Antibodies Clonality Applications Host Species Product code
: MitoSciences product
HIF1 alpha antibody [mgc3] (ab16066)Clonality Applications Host Species cross reactivity M EMSA, GSA, ICC/IF, IHC-P, IP, WB Ms Hu, Cow, Pig
ab16066 staining of HIF1 alpha in human small intestine (IBD) paraformaldehyde-fixed,paraffin-embedded sections by immunohistochemistry.This antibody has been cited in 7 publications and has a rating: Excellent
Hsp90 antibody [AC88] (ab13492)Clonality Applications Host Species cross reactivity M Flow Cyt, ICC/IF, IHC-Fr, IHC-P, Ms Hu, Ms, Rat, Rb, C. elegans, IP, WB Chk, Dog, Shp and more
ICC/IF image of ab13492 stained NIH3T3 mouse fibroblasts (orange).This antibody has been cited in 2 publications and has a rating: Good
HIF3 alpha antibody (ab10134)Clonality Applications Host Species cross reactivity P ICC/IF, IHC-P, IP, WB Rb Hu, Ms
ICC/IF image of ab10134 stained HeLa cells (green).This antibody has been cited in 2 publications and has a rating: Good
Glucose transporter GLUT1 antibody (ab652)Clonality Applications Host Species cross reactivity P ICC/IF, IHC-Fr, IHC-P, IM, IP, WB Rb Hu, Ms, Rt
ICC/IF image of ab652 stained HeLa cells (green).This antibody has been cited in 27 publications and has a rating: Good
VEGF antibody (ab46154)Clonality Applications Host Species cross reactivity P ICC/IF, IHC-FoFr, IHC-P, WB Rb Hu, Ms, Rt
ICC/IF image of ab46154 stained HeLa cells (green).This antibody has been cited in 10 publications and has a rating: Excellent
HIF1 alpha [EP1215Y] M ICC/IF, IHC-P, WB Rb Hu, Rat ab51608HIF1 alpha (Hydroxy P402) P WB Rb Hu ab72775HIF1 alpha (Hydroxy P564) P WB Rb Hu ab72777HIF1 beta / ARNT [2B10] M ICC/IF, IHC-P, IP, WB Ms Hu, Ms, Rat, AGMk ab2771HIF2 alpha P ICC/IF, IHC-P, WB Rb Hu, Rat ab20654HIF3 alpha P ICC/IF, IHC-P, WB Rb Hu, Ms ab10134HIF3 alpha P WB Rb Hu, Ms ab2165SIRT1 M Flow Cyt, ICC/IF, In-Cell ELISA, WB Ms Hu, Ms, Rat ab110304PHD1/prolyl hydroxylase [EPR2] M Flow Cyt, ICC/IF, IHC-P, WB Rb Hu, Ms, Rat ab108980PHD1/prolyl hydroxylase M ICC, IHC-P, IP, WB Rb Hu, Ms, Rat ab113077PHD2 / prolyl hydroxylase [EPR3661] M Flow Cyt, ICC, IHC-P, IP, WB Rb Hu, Ms ab109088PHD3 M IHC-P, WB Ms Hu ab77610SIAH1/2 [8G7H12] M IP, WB Ms Hu, Rat, Dm, Pig, Zfsh ab77167HIF1AN M Flow Cyt, ICC/IF, IHC-P, WB Rb Hu ab92498HIF1AN M ICC/IF, WB Rb Hu ab12289Hsp90 [AC88] M Flow Cyt, ICC/IF, IHC-Fr, IHC-P, IP, WB Ms Hu, Ms, Rat, AGMk, Ce, Carp, Chk, Dog, Fsh, Gpig, Hm, Mk, Pig, Rb, Rtrout, Shp ab13492Elongin B P ICC/IF, IP, WB Rb Hu ab45297TCEB1 (Elongin C) P ICC/IF, WB Ms Hu ab21778Cullin 2 P IHC-P, WB Rb Hu, Ms ab2967Von Hippel Lindau P ELISA, WB Goat Hu ab77262ROC1 P ICC/IF, IHC-P, IP, WB Rb Hu ab86862Beta-Catenin P Hu, Ms, Rat, Xl Rb ICC/IF, IHC-FoFr, IHC-P, WB, sELISA ab16051Vascular endothelial growth factor (VEGF) P ICC/IF, IHC-FoFr, IHC-P, WB Rb Hu, Ms, Rat ab46154VEGF [VG-1] M ELISA, ICC/IF, IHC-Fr, IHC-P, IP, WB Ms Hu, Ms, Rat, Dog ab1316EGF [EGF-2] M ICC/IF, WB Ms Hu ab8282GLUT-1 P ICC/IF, IHC-Fr, IHC-P, IM, IP, WB Rb Hu, Ms, Rat ab652GSK3 Beta [Y174] M ICC, IHC-P, WB Rb Hu, Ms, Rat ab32391Enolase-1 M Flow Cyt, ICC/IF, IP, In-Cell ELISA Ms Hu ab112994iNOS P EM, ICC/IF, IHC-Fr, IHC-P, WB Rb Hu, Ms, Rat ab15323eNOS P ELISA, ICC/IF, IHC-Fr, IHC-P, IP, WB Rb Hu, Ms, Rat ab66127CXCR-4 P Flow Cyt, ICC/IF, IHC-Fr, IHC-P, IP, WB Rb Hu, Ms, Rat ab2074
HIF1 alpha protein (His tag) SDS-PAGE E. coli - ab82065HIF2 alpha BL - - ab21447PHD1/prolyl hydroxylase - - - ab91085Von Hippel Lindau protein (His tag) SDS-PAGE E. coli Hu ab48702
HIF1 alpha antibody panel IHC-Fr, IHC-P, WB Hu, Ms, Rat, Fr, Pig, Rb, Sh ab110304ATP synthase enzyme activity microplate assay kit FuncS Hu, Rat, Cow ab109714Alpha Ketoglutarate (alpha KG) assay kit FuncS Sample type: Tissue culture supernatants, urine, plasma, serum ab83431NADP/NADPH Assay Kit FuncS Sample type: Cell and tissue lysates, culture media, urine, plasma and serum, as well as many other biological fluids ab65349HIF1 / GLUT Hypoxia ICE Kit In-Cell ELISA Hu ab125298HIF1 / PDK1 Hypoxia ICE Kit In-Cell ELISA Hu ab125299HIF1 / Actin Hypoxia ICE Kit In-Cell ELISA Hu ab125300
Panels and assay kits Applications Species Product code
Proteins and peptides Applications Host Species Product code
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