Entry Name FoxO signaling pathway - Mus musculus (house mouse)
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 Mus musculus (house mouse) [GN:
mmu ]
Gene 105787 Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [KO:K07198 ] [EC:2.7.11.31 ]
108079 Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform 1 [KO:K07198 ] [EC:2.7.11.31 ]
108097 Prkab2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
108099 Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform 1 [KO:K07200 ]
12053 Bcl6; B-cell lymphoma 6 protein homolog isoform 1 [KO:K15618 ]
12125 Bcl2l11; bcl-2-like protein 11 isoform 1 [KO:K16341 ]
12176 Bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464 ]
12443 Ccnd1; G1/S-specific cyclin-D1 isoform 2 [KO:K04503 ]
12575 Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
12576 Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
12579 Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685 ]
12581 Cdkn2d; cyclin-dependent kinase 4 inhibitor D isoform 1 [KO:K06623 ]
12675 Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 2 [KO:K04467 ] [EC:2.7.11.10 ]
13197 Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
13609 S1pr1; sphingosine 1-phosphate receptor 1 [KO:K04288 ]
13611 S1pr4; sphingosine 1-phosphate receptor 4 [KO:K04293 ]
13645 Egf; pro-epidermal growth factor isoform 1 preproprotein [KO:K04357 ]
14103 Fasl; tumor necrosis factor ligand superfamily member 6 isoform 1 [KO:K04389 ]
14784 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
14816 Grm1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603 ]
16000 Igf1; insulin-like growth factor I isoform 4 preproprotein [KO:K05459 ]
16150 Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209 ] [EC:2.7.11.10 ]
16193 Il6; interleukin-6 isoform 1 precursor [KO:K05405 ]
16197 Il7r; interleukin-7 receptor subunit alpha isoform 1 precursor [KO:K05072 ]
17127 Smad3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
17128 Smad4; mothers against decapentaplegic homolog 4 isoform 1 [KO:K04501 ]
17873 Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
18706 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform a [KO:K00922 ] [EC:2.7.1.153 ]
18708 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 2 [KO:K02649 ]
18709 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform 1 [KO:K02649 ]
18710 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
19079 Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
19082 Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform 1 [KO:K07200 ]
19374 Rag2; V(D)J recombination-activating protein 2 [KO:K10988 ]
19651 Rbl2; retinoblastoma-like protein 2 isoform 1 [KO:K16332 ]
20528 Slc2a4; solute carrier family 2, facilitated glucose transporter member 4 isoform 1 [KO:K07191 ]
20848 Stat3; signal transducer and activator of transcription 3 isoform 1 [KO:K04692 ]
216439 Agap2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform 1 [KO:K17848 ]
21803 Tgfb1; transforming growth factor beta-1 proprotein preproprotein [KO:K13375 ]
21808 Tgfb2; transforming growth factor beta-2 proprotein isoform 1 preproprotein [KO:K13376 ]
21809 Tgfb3; transforming growth factor beta-3 proprotein precursor [KO:K13377 ]
22035 Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
23882 Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
241113 Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
26395 Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368 ] [EC:2.7.12.2 ]
26396 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369 ] [EC:2.7.12.2 ]
26556 Homer1; homer protein homolog 1 isoform L [KO:K15010 ]
26557 Homer2; homer protein homolog 2 isoform 1 [KO:K15010 ]
26558 Homer3; homer protein homolog 3 isoform 2 [KO:K15010 ]
27401 Skp2; S-phase kinase-associated protein 2 isoform a [KO:K03875 ]
434175 Ccnb1-ps; G2/mitotic-specific cyclin-B1-like [KO:K05868 ]
56486 Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341 ]
57436 Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341 ]
58231 Stk4; serine/threonine-protein kinase 4 precursor [KO:K04411 ]
66822 Fbxo25; F-box only protein 25 isoform 2 [KO:K10305 ]
74769 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
93739 Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [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 KO pathway
