Entry Name FoxO signaling pathway - Trachypithecus francoisi (Francois's langur)
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 Trachypithecus francoisi (Francois's langur) [GN:
tfn ]
Gene 117075968 TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
117074794 TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376 ]
117063892 SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
117070466 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
117089314 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199 ]
117075492 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
117090183 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
117073087 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
117094511 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
117067797 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
117094439 IRS1; LOW QUALITY PROTEIN: insulin receptor substrate 1 [KO:K16172 ]
117077563 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
117083761 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117084122 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
117093348 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
117065206 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
117092662 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
117075022 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
117089864 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848 ]
117066962 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
117069667 SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099 ]
117090585 LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3-like [KO:K21771 ]
117090495 CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624 ]
117098362 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
117092072 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
117075703 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
117074605 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
117083738 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721 ]
117082566 BNIP3; LOW QUALITY PROTEIN: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
117065995 ATG12; LOW QUALITY PROTEIN: ubiquitin-like protein ATG12 [KO:K08336 ]
117088066 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341 ]
117071533 gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
117090562 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [KO:K08341 ]
117072764 gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
117067806 GABARAP; gamma-aminobutyric acid receptor-associated protein [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 LinkDB All DBs
