Entry Name FoxO signaling pathway - Xenopus laevis (African 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 laevis (African clawed frog) [GN:
xla ]
Gene 100127310 prkag3.S; protein kinase, AMP-activated, gamma 3 non-catalytic subunit S homeolog [KO:K07200 ]
101027271 gadd45b.S; growth arrest and DNA damage inducible beta S homeolog [KO:K04402 ]
108696110 bnip3.L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 isoform X1 [KO:K15464 ]
108700276 tgfb1.S; transforming growth factor beta-1 proprotein-like [KO:K13375 ]
108700426 smad4.2.S; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
108706884 pik3r2.S; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
108709817 prkag1.S; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
108712402 gadd45b.L; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
108713027 pik3r2.L; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
108714209 gadd45a.L; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
108715004 faslg.S; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
108715442 gabarapl2.S; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
108715739 prkab2.S; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
108715919 prkab1.L; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199 ]
108717006 tnfsf10.L; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
108717120 pik3cb.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
108717706 tgfb2.S; transforming growth factor beta-2 proprotein-like isoform X1 [KO:K13376 ]
108718090 pik3ca.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
108718190 pik3cb.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
108718729 prkag2.L; protein kinase, AMP-activated, gamma 2 non-catalytic subunit L homeolog [KO:K07200 ]
373752 pik3ca.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
373801 tgfb2.L; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
379224 gadd45a.S; growth arrest and DNA damage inducible alpha S homeolog [KO:K04402 ]
379264 stat3.2.L; signal transducer and activator of transcription 3.2 [KO:K04692 ]
379285 gadd45g.S; uncharacterized protein LOC379285 [KO:K04402 ]
379290 g6pc1.2.S; glucose-6-phosphatase, catalytic subunit 1, gene 2 S homeolog [KO:K01084 ] [EC:3.1.3.9 ]
379852 g6pc1.1.L; glucose-6-phosphatase, catalytic subunit 1, gene 1 L homeolog [KO:K01084 ] [EC:3.1.3.9 ]
379991 map2k1.L; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368 ] [EC:2.7.12.2 ]
380124 prkag3.L; protein kinase, AMP-activated, gamma 3 non-catatlytic subunit [KO:K07200 ]
380316 homer3.L; homer scaffold protein 3 L homeolog [KO:K15010 ]
380372 prkab2.L; protein kinase, AMP-activated, beta 2 non-catalytic subunit L homeolog [KO:K07199 ]
397771 kras.L; kirsten rat sarcoma viral oncogene homolog L homeolog [KO:K07827 ]
397778 tgfb1.L; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
398786 bnip3.S; BCL2/adenovirus E1B 19kDa interacting protein 3 S homeolog [KO:K15464 ]
398855 g6pc1.2.L; glucose-6-phosphatase, catalytic subunit 1, gene 2 L homeolog [KO:K01084 ] [EC:3.1.3.9 ]
398888 ccnb2.L; uncharacterized protein LOC398888 [KO:K21770 ]
398925 stk4.S; serine/threonine-protein kinase 4 [KO:K04411 ]
398958 prkag2.S; protein kinase, AMP-activated, gamma 2 non-catalytic subunit S homeolog [KO:K07200 ]
399172 prkaa2.S; protein kinase, AMP-activated, alpha 2 catalytic subunit S homeolog [KO:K07198 ] [EC:2.7.11.31 ]
399196 gadd45g.L; growth arrest and DNA damage inducible gamma L homeolog [KO:K04402 ]
399202 pik3r1.S; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
399295 tgfbr1.S; transforming growth factor beta receptor I S homeolog precursor [KO:K04674 ] [EC:2.7.11.30 ]
399406 hras.L; Harvey rat sarcoma viral oncogene homolog L homeolog [KO:K02833 ]
399424 pck2.L; phosphoenolpyruvate carboxykinase 2 (mitochondrial) L homeolog [KO:K01596 ] [EC:4.1.1.32 ]
399458 grb2.L; growth factor receptor-bound protein 2-A [KO:K04364 ]
403356 smad4.2.L; SMAD family member 4, gene 2 L homeolog 2 [KO:K04501 ]
414477 gabarap.L; uncharacterized protein LOC414477 [KO:K08341 ]
432121 fbxo25.L; F-box only protein 25 isoform X1 [KO:K10305 ]
432200 ikbkb.L; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta L homeolog [KO:K07209 ] [EC:2.7.11.10 ]
443964 pik3r1.L; phosphoinositide-3-kinase regulatory subunit 1 L homeolog [KO:K02649 ]
443979 gabarapl1.S; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
443998 prkab1.S; protein kinase, AMP-activated, beta 1 non-catalytic subunit S homeolog [KO:K07199 ]
444033 slc2a4.L; solute carrier family 2 (facilitated glucose transporter), member 4 L homeolog [KO:K07191 ]
444095 grb2.S; growth factor receptor-bound protein 2-B [KO:K04364 ]
444397 prkag1.L; protein kinase, AMP-activated, gamma 1 non-catalytic subunit L homeolog [KO:K07200 ]
444659 s1pr1.L; sphingosine-1-phosphate receptor 1 L homeolog [KO:K04288 ]
446719 cdkn2d.S; cyclin-dependent kinase inhibitor 2D S homeolog [KO:K06623 ]
446786 pik3r3.S; phosphoinositide-3-kinase regulatory subunit 3 S homeolog [KO:K02649 ]
446862 bcl6.S; BCL6, transcription repressor S homeolog [KO:K15618 ]
447506 g6pc1.1.S; glucose-6-phosphatase, catalytic subunit 1, gene 1 S homeolog [KO:K01084 ] [EC:3.1.3.9 ]
447594 pik3r3.L; phosphoinositide-3-kinase regulatory subunit 3 L homeolog [KO:K02649 ]
492305 cdkn1a.L; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
492306 cdkn1b.S; cyclin-dependent kinase inhibitor 1B (p27, Kip1) S homeolog [KO:K06624 ]
494762 gabarapl1.L; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
495290 prkaa1.L; protein kinase, AMP-activated, alpha 1 catalytic subunit L homeolog [KO:K07198 ] [EC:2.7.11.31 ]
495412 bcl6.L; BCL6, transcription repressor L homeolog [KO:K15618 ]
594872 homer1.L; homer scaffold protein 1 L homeolog [KO:K15010 ]
734814 gabarapl2.L; GABA(A) receptor-associated protein like 2 L homeolog [KO:K08341 ]
734901 skp2.L; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase L homeolog [KO:K03875 ]
779100 stat3.1.L; signal transducer and activator of transcription 3.1 [KO:K04692 ]
779226 stk4.L; serine/threonine kinase 4 L homeolog [KO:K04411 ]
779240 cdkn2b.L; cyclin-dependent kinase inhibitor 2B L homeolog [KO:K04685 ]
780764 smad4.L; SMAD family member 4, gene 1 L homeolog [KO:K04501 ]
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 
