Entry Name FoxO signaling pathway - Xenopus tropicalis (tropical clawed frog)
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 Xenopus tropicalis (tropical clawed frog) [GN:
xtr ]
Gene 100038054 cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625 ]
100124789 faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
100125135 prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
100125141 gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
100127782 prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
100144924 pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100158499 prkag2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200 ]
100380160 prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
100486835 pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100487013 gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
100493578 tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
100496997 agap2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848 ]
100497001 pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100498278 stat3.1; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
100498547 stat3.2; signal transducer and activator of transcription 3.2 isoform X1 [KO:K04692 ]
101731550 slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
448442 gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
448767 cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685 ]
493272 smad3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
493396 kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
493492 grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
496614 gabarapl1; GABA(A) receptor-associated protein like 1 [KO:K08341 ]
548576 bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
548905 gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
549983 pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
595040 gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
779860 prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
780300 cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623 ]
780355 s1pr1; sphingosine 1-phosphate receptor 1 [KO:K04288 ]
780390 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
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 
