Entry Name FoxO signaling pathway - Nannospalax galili (Upper Galilee mountains blind mole rat)
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 Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:
ngi ]
Gene 103725661 Gabarapl2; GABA type A receptor associated protein like 2 [KO:K08341 ]
103726789 Prkab1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199 ]
103726879 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
103727728 Prkag3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200 ]
103730305 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
103731514 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
103731998 Prkab2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199 ]
103735896 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
103738715 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
103742898 Agap2; ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 [KO:K17848 ]
103743354 Gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402 ]
103743944 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
103745323 Prkag2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200 ]
103745480 Gabarapl1; GABA type A receptor associated protein like 1 [KO:K08341 ]
103750569 Prkag1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200 ]
103751225 Gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402 ]
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
