Entry Name FoxO signaling pathway - Macaca mulatta (rhesus monkey)
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 Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene 100425255 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
100426120 BNIP3; LOW QUALITY PROTEIN: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
106992315 TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375 ]
574128 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
574159 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
693493 HOMER2; homer protein homolog 2 isoform X1 [KO:K15010 ]
694451 TNFSF10; tumor necrosis factor ligand superfamily member 10 precursor [KO:K04721 ]
694534 CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771 ]
695558 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198 ] [EC:2.7.11.31 ]
695737 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
696207 PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596 ] [EC:4.1.1.32 ]
696765 ATG12; LOW QUALITY PROTEIN: ubiquitin-like protein ATG12 [KO:K08336 ]
696992 RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332 ]
697082 BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341 ]
697188 CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
697835 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
698444 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
698619 EGF; pro-epidermal growth factor isoform X2 [KO:K04357 ]
698736 GRM1; metabotropic glutamate receptor 1 precursor [KO:K04603 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
699806 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
699869 IL7R; interleukin-7 receptor subunit alpha [KO:K05072 ]
700617 SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875 ]
701054 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
701803 SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501 ]
702041 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
702782 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200 ]
703239 TGFB3; transforming growth factor beta-3 precursor [KO:K13377 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
707540 TGFB2; transforming growth factor beta-2 precursor [KO:K13376 ]
709209 CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685 ]
709298 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
709511 CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467 ] [EC:2.7.11.10 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
711257 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
711355 SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
712637 S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293 ]
713172 CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623 ]
713777 SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099 ]
714413 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
714597 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
714701 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
715504 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 [KO:K17848 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
716813 S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288 ]
716837 RAG2; V(D)J recombination-activating protein 2 [KO:K10988 ]
717640 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
719199 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
721821 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369 ] [EC:2.7.12.2 ]
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
