Entry
Name
FoxO signaling pathway - Pteropus vampyrus (large flying fox)
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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Pteropus vampyrus (large flying fox) [GN:
pvp ]
Gene
105292297 SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
105289266 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
105297801 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
105297531 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X3 [KO:K07200 ]
105291053 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200 ]
105303778 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
105291195 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
105307215 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105307575 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105308956 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
105296605 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105297140 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
105299371 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
105307392 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848 ]
105306294 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
105293045 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
105293353 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
105298440 CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X4 [KO:K04685 ]
105300252 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
105300424 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
105295887 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
105299797 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
105305707 TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
105300381 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
105305361 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X2 [KO:K08341 ]
105291731 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
105295894 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [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 pathway
KO pathway
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