KEGG   PATHWAY: cjc04068
Entry
cjc04068                    Pathway                                
Name
FoxO signaling pathway - Callithrix jacchus (white-tufted-ear marmoset)
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
Pathway map
cjc04068  FoxO signaling pathway
cjc04068

Other DBs
GO: 0009267
Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100401979  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
100390586  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100392463  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
100389596  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
100404359  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100409302  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100393808  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
100390825  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
100396565  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
100385413  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
100406673  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X3 [KO:K07199]
100409760  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
100394141  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X5 [KO:K07200]
100386781  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X6 [KO:K07200]
100390042  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
100414864  NLK; serine/threonine-protein kinase NLK isoform X1 [KO:K04468] [EC:2.7.11.24]
100393248  SKP2; S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
100415620  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100396301  E3 ubiquitin-protein ligase Mdm2-like isoform X1 [KO:K06643] [EC:2.3.2.27]
100414241  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
100395278  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100405037  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100395149  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100410859  USP7; ubiquitin carboxyl-terminal hydrolase 7 isoform X1 [KO:K11838] [EC:3.4.19.12]
100396530  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
100392721  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100387686  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100390109  MAPK10; mitogen-activated protein kinase 10 isoform X7 [KO:K04440] [EC:2.7.11.24]
100407296  STK4; serine/threonine-protein kinase 4 isoform X1 [KO:K04411]
100394985  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100408399  IGF1R; insulin-like growth factor 1 receptor isoform X3 [KO:K05087] [EC:2.7.10.1]
100393089  INS; insulin [KO:K04526]
100403400  INSR; insulin receptor isoform X4 [KO:K04527] [EC:2.7.10.1]
100387742  IRS1; insulin receptor substrate 1 [KO:K16172]
100404822  IRS2; insulin receptor substrate 2 [KO:K07187]
100410200  IRS4; insulin receptor substrate 4 [KO:K17446]
100403494  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100391655  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
100398849  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100406689  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100392639  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100414659  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100389944  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X4 [KO:K06276] [EC:2.7.11.1]
100393096  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100393460  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100404447  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100399039  AKT3; RAC-gamma serine/threonine-protein kinase isoform X6 [KO:K04456] [EC:2.7.11.1]
100388080  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100389266  SGK1; serine/threonine-protein kinase Sgk1 isoform X3 [KO:K13302] [EC:2.7.11.1]
100396756  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
100387916  SGK3; serine/threonine-protein kinase Sgk3 isoform X1 [KO:K13304] [EC:2.7.11.1]
100397393  FOXO1; forkhead box protein O1 [KO:K07201]
100406446  FOXO3; LOW QUALITY PROTEIN: forkhead box protein O3 [KO:K09408]
100384968  FOXO4; forkhead box protein O4 [KO:K12358]
100409867  FOXO6; forkhead box protein O6 [KO:K17847]
100410312  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
100389882  HOMER3; homer protein homolog 3 isoform X1 [KO:K15010]
100392638  HOMER1; homer protein homolog 1 isoform X2 [KO:K15010]
100396179  HOMER2; homer protein homolog 2 isoform X6 [KO:K15010]
100407586  AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848]
100407384  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
100393440  IL6; interleukin-6 precursor [KO:K05405]
100386149  IL10; interleukin-10 [KO:K05443]
100389282  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
100388651  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100412158  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100395682  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100414931  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100410124  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100406017  HRAS; GTPase HRas [KO:K02833]
118144179  KRAS; GTPase KRas isoform X2 [KO:K07827]
100414782  NRAS; GTPase NRas isoform X2 [KO:K07828]
108591807  GTPase NRas-like [KO:K07828]
100403091  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
100415300  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100387961  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
100387394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100393991  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100400700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100404815  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100396611  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100396967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100404377  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100405093  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100398703  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100390972  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
100390772  uncharacterized protein LOC100390772 isoform X1 [KO:K09385]
128928041  FOXG1; forkhead box protein G1 [KO:K09385]
100391291  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
100388085  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1-like [KO:K05868]
100388842  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
100394742  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
103796419  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100390172  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100392397  CCNG2; cyclin-G2 [KO:K10146]
100392363  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100410795  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
100894215  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100387508  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100410298  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100409054  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100409089  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
100393070  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
100395177  PLK4; serine/threonine-protein kinase PLK4 isoform X2 [KO:K08863] [EC:2.7.11.21]
100412572  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100405303  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100394399  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
100404850  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100399968  BCL2L11; bcl-2-like protein 11 isoform X16 [KO:K16341]
100396000  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
100413256  BCL6; B-cell lymphoma 6 protein [KO:K15618]
100415154  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
100396359  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
100404267  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
100393860  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
100399942  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
100410093  gamma-aminobutyric acid receptor-associated protein-like [KO:K08341]
100411187  gamma-aminobutyric acid receptor-associated protein-like [KO:K08341]
100388372  CAT; catalase [KO:K03781] [EC:1.11.1.6]
100410185  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
100402387  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100404441  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
100404870  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X2 [KO:K01596] [EC:4.1.1.32]
100415213  G6PC1; glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
100400291  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
100400025  G6PC3; glucose-6-phosphatase 3 isoform X2 [KO:K01084] [EC:3.1.3.9]
100397720  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
100388178  KLF2; Krueppel-like factor 2 [KO:K17845]
100413093  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
100395720  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
100396079  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
100398284  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
100387690  FBXO32; F-box only protein 32 [KO:K10305]
Compound
C00008  ADP
C00020  AMP
C00025  L-Glutamate
C00031  D-Glucose
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
J Endocrinol 193:195-207 (2007)
DOI:10.1677/JOE-06-0191
Reference
  Authors
van der Horst A, Burgering BM
  Title
Stressing the role of FoxO proteins in lifespan and disease.
  Journal
Nat Rev Mol Cell Biol 8:440-50 (2007)
DOI:10.1038/nrm2190
Reference
  Authors
Zhang X, Tang N, Hadden TJ, Rishi AK
  Title
Akt, FoxO and regulation of apoptosis.
  Journal
Biochim Biophys Acta 1813:1978-86 (2011)
DOI:10.1016/j.bbamcr.2011.03.010
Reference
  Authors
Eijkelenboom A, Burgering BM
  Title
FOXOs: signalling integrators for homeostasis maintenance.
  Journal
Nat Rev Mol Cell Biol 14:83-97 (2013)
DOI:10.1038/nrm3507
Reference
  Authors
Daitoku H, Fukamizu A
  Title
FOXO transcription factors in the regulatory networks of longevity.
  Journal
J Biochem 141:769-74 (2007)
DOI:10.1093/jb/mvm104
Reference
  Authors
Hedrick SM
  Title
The cunning little vixen: Foxo and the cycle of life and death.
  Journal
Nat Immunol 10:1057-63 (2009)
DOI:10.1038/ni.1784
Reference
  Authors
Coffer PJ, Burgering BM
  Title
Forkhead-box transcription factors and their role in the immune system.
  Journal
Nat Rev Immunol 4:889-99 (2004)
DOI:10.1038/nri1488
Reference
  Authors
Ro SH, Liu D, Yeo H, Paik JH
  Title
FoxOs in neural stem cell fate decision.
  Journal
Arch Biochem Biophys 534:55-63 (2013)
DOI:10.1016/j.abb.2012.07.017
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins.
  Journal
Trends Mol Med 14:219-27 (2008)
DOI:10.1016/j.molmed.2008.03.002
Reference
  Authors
Hagenbuchner J, Ausserlechner MJ
  Title
Mitochondria and FOXO3: breath or die.
  Journal
Front Physiol 4:147 (2013)
DOI:10.3389/fphys.2013.00147
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
"Sly as a FOXO": new paths with Forkhead signaling in the brain.
  Journal
Curr Neurovasc Res 4:295-302 (2007)
DOI:10.2174/156720207782446306
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
J Biol Chem 287:30436-43 (2012)
DOI:10.1074/jbc.M112.359661
Reference
  Authors
Huang H, Tindall DJ
  Title
Regulation of FOXO protein stability via ubiquitination and proteasome degradation.
  Journal
Biochim Biophys Acta 1813:1961-4 (2011)
DOI:10.1016/j.bbamcr.2011.01.007
Reference
  Authors
Greer EL, Brunet A
  Title
FOXO transcription factors at the interface between longevity and tumor suppression.
  Journal
Oncogene 24:7410-25 (2005)
DOI:10.1038/sj.onc.1209086
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
Cell 117:211-23 (2004)
DOI:10.1016/S0092-8674(04)00298-3
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
Mol Cell 32:221-31 (2008)
DOI:10.1016/j.molcel.2008.09.013
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
Nat Cell Biol 8:1064-73 (2006)
DOI:10.1038/ncb1469
Reference
  Authors
Zhang Y, Gan B, Liu D, Paik JH
  Title
FoxO family members in cancer.
  Journal
Cancer Biol Ther 12:253-9 (2011)
DOI:10.4161/cbt.12.4.15954
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
Biochem J 380:297-309 (2004)
DOI:10.1042/BJ20040167
Related
pathway
cjc00010  Glycolysis / Gluconeogenesis
cjc00020  Citrate cycle (TCA cycle)
cjc00190  Oxidative phosphorylation
cjc04010  MAPK signaling pathway
cjc04110  Cell cycle
cjc04120  Ubiquitin mediated proteolysis
cjc04140  Autophagy - animal
cjc04151  PI3K-Akt signaling pathway
cjc04210  Apoptosis
cjc04350  TGF-beta signaling pathway
cjc04630  JAK-STAT signaling pathway
cjc04910  Insulin signaling pathway
KO pathway
ko04068   
LinkDB

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