Entry Name FoxO signaling pathway - Canis lupus familiaris (dog)
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 Other DBs Organism Canis lupus familiaris (dog) [GN:
cfa ]
Gene 100174780 TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
100855728 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402 ]
100856379 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
403429 CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
403657 EGF; pro-epidermal growth factor precursor [KO:K04357 ]
403673 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
403998 TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
442968 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
474636 ATG12; ubiquitin-like protein ATG12 isoform X2 [KO:K08336 ]
474890 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
475546 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
476196 SMAD4; mothers against decapentaplegic homolog 4 isoform X2 [KO:K04501 ]
477085 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
477240 STK4; serine/threonine-protein kinase 4 isoform X2 [KO:K04411 ]
477796 CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467 ] [EC:2.7.11.10 ]
478127 RBL2; retinoblastoma-like protein 2 isoform X2 [KO:K16332 ]
479351 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198 ] [EC:2.7.11.31 ]
479479 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
479646 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341 ]
481130 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X2 [KO:K17848 ]
481563 CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685 ]
482839 IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209 ] [EC:2.7.11.10 ]
483312 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
483419 RAG2; V(D)J recombination-activating protein 2 [KO:K10988 ]
484024 GRM1; metabotropic glutamate receptor 1 isoform X2 [KO:K04603 ]
484198 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
484648 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366 ] [EC:2.7.11.1 ]
484813 HOMER3; homer protein homolog 3 isoform X1 [KO:K15010 ]
485069 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
485548 IRS2; insulin receptor substrate 2 isoform X8 [KO:K07187 ]
486295 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
486559 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
487235 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
488084 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
488526 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
488596 TGFB2; transforming growth factor beta-2 proprotein isoform X3 [KO:K13376 ]
488933 HOMER1; homer protein homolog 1 isoform X3 [KO:K15010 ]
489228 SKP2; S-phase kinase-associated protein 2 isoform X5 [KO:K03875 ]
489571 PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X2 [KO:K07198 ] [EC:2.7.11.31 ]
489644 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922 ] [EC:2.7.1.153 ]
490682 SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099 ]
490796 TGFB3; transforming growth factor beta-3 proprotein [KO:K13377 ]
490967 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
607408 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 isoform X2 [KO:K15464 ]
609956 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
610255 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
610902 SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
611216 CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623 ]
612082 S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293 ]
612582 IL7R; interleukin-7 receptor subunit alpha isoform X2 [KO:K05072 ]
612867 BCL2L11; bcl-2-like protein 11 isoform X4 [KO:K16341 ]
612919 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
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
