Entry Name FoxO signaling pathway - Orcinus orca (killer whale)
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 Other DBs Organism Orcinus orca (killer whale) [GN:
oor ]
Gene 101269256 GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
101269890 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200 ]
101269962 STK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase 4 [KO:K04411 ]
101270605 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X2 [KO:K07199 ]
101272436 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
101273257 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X2 [KO:K07191 ]
101274009 GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
101276254 TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376 ]
101277568 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
101278075 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101278512 CCNB3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771 ]
101278974 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
101279528 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
101281352 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649 ]
101281369 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
101281489 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
101281934 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
101282902 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X2 [KO:K04721 ]
101283011 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101283103 AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848 ]
101285437 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101285919 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402 ]
101286197 TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375 ]
101286740 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
101288065 GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
101288074 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
101288264 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
101289338 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
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
