KEGG   PATHWAY: cqd04068
Entry
cqd04068                    Pathway                                
Name
FoxO signaling pathway - Cherax quadricarinatus (Australian red claw crayfish)
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
cqd04068  FoxO signaling pathway
cqd04068

Other DBs
GO: 0009267
Organism
Cherax quadricarinatus (Australian red claw crayfish) [GN:cqd]
Gene
128702861  TGF-beta receptor type-1-like isoform X1 [KO:K04674] [EC:2.7.11.30]
128687072  mothers against decapentaplegic homolog 4-like [KO:K04501]
128699137  LOW QUALITY PROTEIN: serine/threonine-protein kinase stk11-like [KO:K07298] [EC:2.7.11.1]
128686590  5'-AMP-activated protein kinase catalytic subunit alpha-2-like [KO:K07198] [EC:2.7.11.31]
128702486  5'-AMP-activated protein kinase subunit beta-1-like [KO:K07199]
128693579  serine/threonine-protein kinase NLK-like [KO:K04468] [EC:2.7.11.24]
128689758  S-phase kinase-associated protein 2-like isoform X1 [KO:K03875]
128688377  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
128684996  NAD-dependent protein deacetylase sirtuin-1-like [KO:K11411] [EC:2.3.1.286]
128700699  ubiquitin carboxyl-terminal hydrolase 7-like [KO:K11838] [EC:3.4.19.12]
128688052  LOW QUALITY PROTEIN: stress-activated protein kinase JNK-like [KO:K04440] [EC:2.7.11.24]
128685185  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
128706302  LOW QUALITY PROTEIN: insulin-like [KO:K04526]
128690674  insulin receptor-like [KO:K04527] [EC:2.7.10.1]
128687210  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
128700515  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
128685383  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
128698231  3-phosphoinositide-dependent protein kinase 1-like [KO:K06276] [EC:2.7.11.1]
128699630  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
128701272  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
128695808  LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase A-like [KO:K04456] [EC:2.7.11.1]
128702901  RAC-beta serine/threonine-protein kinase B-like [KO:K04456] [EC:2.7.11.1]
128686473  serine/threonine-protein kinase Sgk2-like [KO:K13302] [EC:2.7.11.1]
128703013  homer protein homolog 2-like isoform X1 [KO:K15010]
128685061  casein kinase I-like isoform X1 [KO:K08960] [EC:2.7.11.1]
128691614  LOW QUALITY PROTEIN: epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
128702299  growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
128695268  son of sevenless homolog 2-like [KO:K03099]
128697738  GTPase HRas [KO:K07827]
128701353  serine/threonine-protein kinase A-Raf-like isoform X1 [KO:K04365] [EC:2.7.11.1]
128688153  dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
128687395  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
128688114  mitogen-activated protein kinase 14-like [KO:K04441] [EC:2.7.11.24]
128694300  protein arginine N-methyltransferase 1-like isoform X1 [KO:K11434] [EC:2.1.1.319]
128694373  fork head domain transcription factor slp1-like [KO:K09385]
128694374  fork head domain transcription factor slp1-like [KO:K09385]
128701304  G2/mitotic-specific cyclin-B2-like isoform X1 [KO:K21770]
128689311  G2/mitotic-specific cyclin-B3-like [KO:K21771]
128685329  G1/S-specific cyclin-D2-like [KO:K10151]
128688578  LOW QUALITY PROTEIN: G1/S-specific cyclin-D2-like [KO:K10151]
128701360  cyclin G-like [KO:K10146]
128694442  serine/threonine-protein kinase PLK1-like [KO:K06631] [EC:2.7.11.21]
128695629  serine/threonine-protein kinase plk-1-like [KO:K08861] [EC:2.7.11.21]
128691913  autophagy protein 12-like [KO:K08336]
128702502  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
128692961  gamma-aminobutyric acid receptor-associated protein-like [KO:K08341]
128685024  catalase-like [KO:K03781] [EC:1.11.1.6]
128696097  superoxide dismutase [Mn], mitochondrial-like [KO:K04564] [EC:1.15.1.1]
128701966  superoxide dismutase [Mn], mitochondrial isoform X1 [KO:K04564] [EC:1.15.1.1]
128702685  phosphoenolpyruvate carboxykinase, cytosolic [GTP]-like [KO:K01596] [EC:4.1.1.32]
128702687  phosphoenolpyruvate carboxykinase, cytosolic [GTP]-like [KO:K01596] [EC:4.1.1.32]
128686171  glucose-6-phosphatase 3-like isoform X1 [KO:K01084] [EC:3.1.3.9]
128688570  Krueppel-like factor 5 [KO:K17845]
128704696  F-box only protein 25-like [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
cqd00010  Glycolysis / Gluconeogenesis
cqd00020  Citrate cycle (TCA cycle)
cqd00190  Oxidative phosphorylation
cqd04120  Ubiquitin mediated proteolysis
cqd04140  Autophagy - animal
cqd04350  TGF-beta signaling pathway
KO pathway
ko04068   
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