Entry Name FoxO signaling pathway - Hemiscyllium ocellatum (epaulette shark)
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 Hemiscyllium ocellatum (epaulette shark) [GN:
hoc ]
Gene 132818019 tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377 ]
132805608 smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
132834303 smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605 ]
132818719 5'-AMP-activated protein kinase subunit beta-2-like isoform X1 [KO:K07199 ]
132827183 5'-AMP-activated protein kinase subunit beta-1-like isoform X1 [KO:K07199 ]
132817720 prkag3a; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
132805847 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
132815848 prkag2a; 5'-AMP-activated protein kinase subunit gamma-2a isoform X1 [KO:K07200 ]
132835334 solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191 ]
132833826 pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
132821912 pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
132822331 pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
132819107 pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649 ]
132830988 stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
132818730 growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402 ]
132828347 growth arrest and DNA damage-inducible protein GADD45 gamma-like [KO:K04402 ]
132828798 growth arrest and DNA damage-inducible protein GADD45 beta-like [KO:K04402 ]
132818661 tumor necrosis factor ligand superfamily member 6-like isoform X1 [KO:K04389 ]
132818663 tumor necrosis factor ligand superfamily member 6-like [KO:K04389 ]
132818664 faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
132821806 tumor necrosis factor ligand superfamily member 10-like [KO:K04721 ]
132824729 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15464 ]
132826245 bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
132823672 gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [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
