Entry
Name
FoxO signaling pathway - Theropithecus gelada (gelada)
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
Theropithecus gelada (gelada) [GN:
tge ]
Gene
112611379 SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
112628064 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
112618609 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
112634124 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
112620461 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
112636403 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
112634045 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
112609908 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
112618874 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
112634042 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
112619294 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
112614522 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
112625914 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
112612001 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
112634053 AGAP2; LOW QUALITY PROTEIN: arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 [KO:K17848 ]
112608953 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
112608918 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
112628758 SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099 ]
112612394 MAP2K2; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
112607789 CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685 ]
112623750 CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625 ]
112634261 CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624 ]
112608708 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
112611273 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402 ]
112612483 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402 ]
112636918 FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389 ]
112618898 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721 ]
112631172 BNIP3; LOW QUALITY PROTEIN: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
112625761 ATG12; LOW QUALITY PROTEIN: ubiquitin-like protein ATG12 [KO:K08336 ]
112613697 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
112608982 GABARAP; gamma-aminobutyric acid receptor-associated protein isoform X1 [KO:K08341 ]
112633963 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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