Entry Name FoxO signaling pathway - Rattus norvegicus (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 Rattus norvegicus (rat) [GN:
rno ]
Gene 114851 Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
120098596 Gabarapl4; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
24414 Grm1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
246775 Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
25112 Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
25125 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
25139 Slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
25164 Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685 ]
25313 Egf; pro-epidermal growth factor precursor [KO:K04357 ]
25385 Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
25520 Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
25631 Smad3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
25717 Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377 ]
25718 Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087 ] [EC:2.7.10.1 ]
291005 Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
294790 Skp2; S-phase kinase-associated protein 2 [KO:K03875 ]
294797 Il7r; interleukin-7 receptor subunit alpha precursor [KO:K05072 ]
295953 Rag2; V(D)J recombination-activating protein 2 [KO:K10988 ]
29733 S1pr1; sphingosine 1-phosphate receptor 1 [KO:K04288 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
299626 Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
301518 Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
314649 S1pr4; sphingosine 1-phosphate receptor 4 [KO:K04293 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
373545 Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform 1 [KO:K07200 ]
494444 Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623 ]
50554 Smad4; mothers against decapentaplegic homolog 4 [KO:K04501 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
58974 Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
59086 Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
64562 Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
64670 Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341 ]
65218 Agap2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 [KO:K17848 ]
689161 Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
81504 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
81809 Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
83571 Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
83803 Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
84480 Bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
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
