KEGG   PATHWAY: npd04068
Entry
npd04068                    Pathway                                
Name
FoxO signaling pathway - Nothoprocta perdicaria (Chilean tinamou)
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
npd04068  FoxO signaling pathway
npd04068

Other DBs
GO: 0009267
Organism
Nothoprocta perdicaria (Chilean tinamou) [GN:npd]
Gene
112942339  [KO:K06625]
112942349  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112942428  IL6; interleukin-6 [KO:K05405]
112942696  [KO:K02649]
112942865  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
112943469  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
112943474  CAT; catalase [KO:K03781] [EC:1.11.1.6]
112943480  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
112943487  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
112943529  HRAS; GTPase HRas [KO:K02833]
112943546  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
112943551  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
112943710  PLK3; serine/threonine-protein kinase PLK3 isoform X1 [KO:K08862] [EC:2.7.11.21]
112943740  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
112943759  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
112943851  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
112943910  KLF2; Krueppel-like factor 2 [KO:K17845]
112943951  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112944080  HOMER1; homer protein homolog 1 [KO:K15010]
112944195  [KO:K13304] [EC:2.7.11.1]
112944410  [KO:K04685]
112944417  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
112944527  IRS4; insulin receptor substrate 4 [KO:K07187]
112944638  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
112944654  IL10; interleukin-10 [KO:K05443]
112944716  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 isoform X1 [KO:K15464]
112944968  RBL2; retinoblastoma-like protein 2 [KO:K16332]
112945115  [KO:K09408]
112945131  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
112945237  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112945254  INS; insulin [KO:K04526]
112945540  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
112945566  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
112945578  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
112945628  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
112945900  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
112945932  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112946009  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
112946045  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
112946216  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
112946445  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
112946628  IGF1; insulin-like growth factor I [KO:K05459]
112946839  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
112946902  HOMER3; homer protein homolog 3 isoform X1 [KO:K15010]
112946923  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
112947033  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
112947233  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
112947476  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
112947731  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
112947867  IRS1; insulin receptor substrate 1 [KO:K16172]
112947911  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112948263  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112948275  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
112948290  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
112948417  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]
112948431  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
112948432  DEPP1; protein DEPP1 [KO:K27679]
112948651  FOXO4; forkhead box protein O4 [KO:K12358]
112948774  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112948967  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112949039  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
112949082  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
112949088  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112949472  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
112949613  STK4; serine/threonine-protein kinase 4 [KO:K04411]
112949644  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
112950140  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
112950210  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
112950258  CCNG2; cyclin-G2 isoform X1 [KO:K10146]
112950296  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
112950669  KRAS; GTPase KRas [KO:K07827]
112950766  [KO:K17847]
112951116  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
112951177  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
112951178  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
112951314  [KO:K09408]
112951338  FBXO32; F-box only protein 32 [KO:K10305]
112951356  BCL2L11; bcl-2-like protein 11 [KO:K16341]
112951378  [KO:K04685]
112951487  NRAS; GTPase NRas [KO:K07828]
112951799  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
112951815  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
112951938  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
112951956  GRM1; metabotropic glutamate receptor 1 [KO:K04603]
112952259  AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 [KO:K17848]
112952326  BCL6; B-cell lymphoma 6 protein isoform X1 [KO:K15618]
112952453  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
112952569  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112952606  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
112952817  HOMER2; homer protein homolog 2 [KO:K15010]
112952880  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
112953017  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112953156  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
112953186  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
112953666  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112953853  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
112954523  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112954606  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
112954908  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
112954963  [KO:K04388] [EC:2.7.11.30]
112955150  TGFB2; transforming growth factor beta-2 [KO:K13376]
112955244  SOS1; son of sevenless homolog 1 [KO:K03099]
112955351  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112955491  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112955595  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
112955675  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
112955737  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
112955779  [KO:K08341]
112956827  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112957256  EGF; pro-epidermal growth factor [KO:K04357]
112957763  SOS2; son of sevenless homolog 2 [KO:K03099]
112957988  FOXG1; forkhead box protein G1 [KO:K09385]
112958062  TGFB3; transforming growth factor beta-3 [KO:K13377]
112958102  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
112958161  PLK4; serine/threonine-protein kinase PLK4 [KO:K08863] [EC:2.7.11.21]
112958826  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
112958909  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
112959234  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112959267  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112959314  FOXO1; forkhead box protein O1 [KO:K07201]
112959404  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
112959596  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112959724  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
112959727  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112959758  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
112959937  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
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
npd00010  Glycolysis / Gluconeogenesis
npd00020  Citrate cycle (TCA cycle)
npd00190  Oxidative phosphorylation
npd04010  MAPK signaling pathway
npd04110  Cell cycle
npd04120  Ubiquitin mediated proteolysis
npd04140  Autophagy - animal
npd04210  Apoptosis
npd04350  TGF-beta signaling pathway
npd04910  Insulin signaling pathway
KO pathway
ko04068   

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