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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
21803 Tgfb1; transforming growth factor, beta 1 [KO:K13375 ]
21808 Tgfb2; transforming growth factor, beta 2 [KO:K13376 ]
21809 Tgfb3; transforming growth factor, beta 3 [KO:K13377 ]
19079 Prkab1; protein kinase, AMP-activated, beta 1 non-catalytic subunit [KO:K07199 ]
108097 Prkab2; protein kinase, AMP-activated, beta 2 non-catalytic subunit [KO:K07199 ]
19082 Prkag1; protein kinase, AMP-activated, gamma 1 non-catalytic subunit [KO:K07200 ]
241113 Prkag3; protein kinase, AMP-activated, gamma 3 non-catalytic subunit [KO:K07200 ]
108099 Prkag2; protein kinase, AMP-activated, gamma 2 non-catalytic subunit [KO:K07200 ]
27401 Skp2; S-phase kinase-associated protein 2 [KO:K03875 ]
20528 Slc2a4; solute carrier family 2 (facilitated glucose transporter), member 4 [KO:K07191 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
14816 Grm1; glutamate receptor, metabotropic 1 [KO:K04603 ]
216439 Agap2; ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 [KO:K17848 ]
20848 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
14784 Grb2; growth factor receptor bound protein 2 [KO:K04364 ]
20662 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
20663 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
12579 Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685 ]
12581 Cdkn2d; cyclin dependent kinase inhibitor 2D [KO:K06623 ]
12575 Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
12576 Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624 ]
19651 Rbl2; RB transcriptional corepressor like 2 [KO:K16332 ]
13197 Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402 ]
17873 Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402 ]
23882 Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402 ]
22035 Tnfsf10; tumor necrosis factor (ligand) superfamily, member 10 [KO:K04721 ]
12176 Bnip3; BCL2/adenovirus E1B interacting protein 3 [KO:K15464 ]
57436 Gabarapl1; GABA type A receptor associated protein like 1 [KO:K08341 ]
56486 Gabarap; gamma-aminobutyric acid receptor associated protein [KO:K08341 ]
93739 Gabarapl2; GABA type A receptor associated protein like 2 [KO:K08341 ]
16598 Klf2; Kruppel-like transcription factor 2 (lung) [KO:K17845 ]
13609 S1pr1; sphingosine-1-phosphate receptor 1 [KO:K04288 ]
13611 S1pr4; sphingosine-1-phosphate receptor 4 [KO:K04293 ]
19374 Rag2; recombination activating gene 2 [KO:K10988 ]
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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