Entry Name FoxO signaling pathway - Ovis aries (sheep)
Description The forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative stress resistance, and longevity. A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. In contrast, the stress-activated c-Jun N-terminal kinase (JNK) and the energy sensing AMP-activated protein kinase (AMPK), upon oxidative and nutrient stress stimuli phosphorylate and activate FoxOs. Aside from PKB, JNK and AMPK, FOXOs are regulated by multiple players through several post-translational modifications, including phosphorylation, but also acetylation, methylation and ubiquitylation.
Class Environmental Information Processing; Signal transductionBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Ovis aries (sheep) [GN:
oas ]
Gene 443417 TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
554322 TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376 ]
554323 TGFB3; transforming growth factor beta-3 proprotein [KO:K13377 ]
443171 SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501 ]
443169 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
101113114 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
101107899 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
100142674 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
101103143 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X3 [KO:K07200 ]
101104483 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X5 [KO:K07200 ]
101118797 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
443318 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
101109759 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101110015 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101117348 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922 ] [EC:2.7.1.153 ]
101123247 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101111546 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649 ]
101121455 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
780484 IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209 ] [EC:2.7.11.10 ]
443101 GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603 ]
443063 HOMER1; homer protein homolog 1 isoform X4 [KO:K15010 ]
100294659 STAT3; signal transducer and activator of transcription 3 isoform X10 [KO:K04692 ]
101109893 GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364 ]
101115240 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
100885762 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
101120573 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
100135696 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
101114153 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721 ]
101108441 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
101118285 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
101118469 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
101117406 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X2 [KO:K08341 ]
101111126 IL7R; interleukin-7 receptor subunit alpha isoform X3 [KO:K05072 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Glauser DA, Schlegel W
Title The emerging role of FOXO transcription factors in pancreatic beta cells.
Journal Reference Authors van der Horst A, Burgering BM
Title Stressing the role of FoxO proteins in lifespan and disease.
Journal Reference Authors Zhang X, Tang N, Hadden TJ, Rishi AK
Title Akt, FoxO and regulation of apoptosis.
Journal Reference Authors Eijkelenboom A, Burgering BM
Title FOXOs: signalling integrators for homeostasis maintenance.
Journal Reference Authors Daitoku H, Fukamizu A
Title FOXO transcription factors in the regulatory networks of longevity.
Journal Reference Authors Hedrick SM
Title The cunning little vixen: Foxo and the cycle of life and death.
Journal Reference Authors Coffer PJ, Burgering BM
Title Forkhead-box transcription factors and their role in the immune system.
Journal Reference Authors Ro SH, Liu D, Yeo H, Paik JH
Title FoxOs in neural stem cell fate decision.
Journal Reference Authors Maiese K, Chong ZZ, Shang YC
Title OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins.
Journal Reference Authors Hagenbuchner J, Ausserlechner MJ
Title Mitochondria and FOXO3: breath or die.
Journal Reference Authors Maiese K, Chong ZZ, Shang YC
Title "Sly as a FOXO": new paths with Forkhead signaling in the brain.
Journal Reference Authors Oh HM, Yu CR, Dambuza I, Marrero B, Egwuagu CE
Title STAT3 protein interacts with Class O Forkhead transcription factors in the cytoplasm and regulates nuclear/cytoplasmic localization of FoxO1 and FoxO3a proteins in CD4(+) T cells.
Journal Reference Authors Huang H, Tindall DJ
Title Regulation of FOXO protein stability via ubiquitination and proteasome degradation.
Journal Reference Authors Greer EL, Brunet A
Title FOXO transcription factors at the interface between longevity and tumor suppression.
Journal Reference Authors Seoane J, Le HV, Shen L, Anderson SA, Massague J
Title Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
Journal Reference Authors Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y, Fukamizu A
Title Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.
Journal Reference Authors van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM
Title FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
Journal Reference Authors Zhang Y, Gan B, Liu D, Paik JH
Title FoxO family members in cancer.
Journal Reference Authors Van Der Heide LP, Hoekman MF, Smidt MP
Title The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.
Journal Related KO pathway LinkDB All DBs
