KEGG   PATHWAY: csec04068
Entry
csec04068                   Pathway                                
Name
FoxO signaling pathway - Cryptotermes secundus (drywood termite)
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
csec04068  FoxO signaling pathway
csec04068

Other DBs
GO: 0009267
Organism
Cryptotermes secundus (drywood termite) [GN:csec]
Gene
111861802  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
111867391  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
111865009  serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
111865905  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X3 [KO:K07198] [EC:2.7.11.31]
111862712  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
111862597  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
111875250  serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
111872935  S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
111871043  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
111870880  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
111868517  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
111873120  ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
111871173  stress-activated protein kinase JNK [KO:K04440] [EC:2.7.11.24]
111861959  insulin-like growth factor [KO:K05459]
111861297  LIRP [KO:K04526]
111862713  uncharacterized protein LOC111862713 [KO:K04526]
111861850  insulin-like peptide receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
111863536  insulin-like receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
111867485  insulin receptor substrate 1 isoform X1 [KO:K16172]
111873335  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111865305  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111867061  phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
111875189  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
111867624  3-phosphoinositide-dependent protein kinase 1 isoform X2 [KO:K06276] [EC:2.7.11.1]
111866549  inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
111871175  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
111874177  RAC serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111869563  serine/threonine-protein kinase Sgk1 [KO:K13304] [EC:2.7.11.1]
111867211  forkhead box protein O isoform X2 [KO:K09408]
111864910  metabotropic glutamate receptor 1 [KO:K04603]
111863640  homer protein homolog 2 [KO:K15010]
111873129  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
111861232  protein enhancer of sevenless 2B [KO:K04364]
111873103  protein son of sevenless [KO:K03099]
111875773  GTPase HRas [KO:K07827]
111870385  GTPase HRas [KO:K07827]
111872156  raf homolog serine/threonine-protein kinase Raf [KO:K04365] [EC:2.7.11.1]
111874579  dual specificity mitogen-activated protein kinase kinase dSOR1 [KO:K04368] [EC:2.7.12.2]
111868600  dual specificity mitogen-activated protein kinase kinase dSOR1 isoform X1 [KO:K04368] [EC:2.7.12.2]
111866618  mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
111868512  mitogen-activated protein kinase p38b isoform X1 [KO:K04441] [EC:2.7.11.24]
111869617  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
111866744  protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
111874987  fork head domain transcription factor slp2 [KO:K09385]
111864820  G2/mitotic-specific cyclin-B [KO:K05868]
111863136  G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
111865733  G1/S-specific cyclin-D2 [KO:K10151]
111861374  G1/S-specific cyclin-D2 [KO:K10151]
111873760  cyclin G [KO:K10146]
111870931  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
111862822  serine/threonine-protein kinase polo [KO:K06631] [EC:2.7.11.21]
111864705  serine/threonine-protein kinase PLK1 [KO:K08861] [EC:2.7.11.21]
111868005  serine/threonine-protein kinase PLK4 isoform X1 [KO:K08863] [EC:2.7.11.21]
111869565  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111866254  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
111873430  autophagy protein 12-like [KO:K08336]
111861481  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
111861276  catalase isoform X1 [KO:K03781] [EC:1.11.1.6]
111861593  catalase [KO:K03781] [EC:1.11.1.6]
111870470  catalase [KO:K03781] [EC:1.11.1.6]
111874691  superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
111874905  serine-protein kinase ATM isoform X2 [KO:K04728] [EC:2.7.11.1]
111872108  phosphoenolpyruvate carboxykinase [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
111870900  glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
111868628  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
csec00010  Glycolysis / Gluconeogenesis
csec00020  Citrate cycle (TCA cycle)
csec00190  Oxidative phosphorylation
csec04120  Ubiquitin mediated proteolysis
csec04140  Autophagy - animal
csec04350  TGF-beta signaling pathway
KO pathway
ko04068   
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