Entry Name FoxO signaling pathway - Myotis lucifugus (little brown bat)
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 Myotis lucifugus (little brown bat) [GN:
mlf ]
Gene 102419263 SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
102427892 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
102430132 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
102430862 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
102428212 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
102425288 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
102436674 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
102419367 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191 ]
102429074 IRS2; LOW QUALITY PROTEIN: insulin receptor substrate 2 [KO:K07187 ]
102418401 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
102422649 PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
102441064 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102433534 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102427890 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649 ]
102441522 LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649 ]
102429230 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
102426106 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
102419324 LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649 ]
102422692 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 [KO:K17848 ]
102422489 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
102421027 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
102441382 CCNB2; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B2 [KO:K21770 ]
102439094 CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625 ]
102428736 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
102427327 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
102429644 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
102439228 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
102441820 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721 ]
102430657 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
102430514 gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
102428870 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X2 [KO:K08341 ]
102418213 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
102436608 S1PR4; LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 4 [KO:K04293 ]
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
