KEGG   PATHWAY: dpa04068
Entry
dpa04068                    Pathway                                
Name
FoxO signaling pathway - Dendroctonus ponderosae (mountain pine beetle)
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
dpa04068  FoxO signaling pathway
dpa04068

Other DBs
GO: 0009267
Organism
Dendroctonus ponderosae (mountain pine beetle) [GN:dpa]
Gene
109542240  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
109537984  mothers against decapentaplegic homolog 4 [KO:K04501]
109540540  mothers against decapentaplegic homolog 4 [KO:K04501]
109536357  mothers against decapentaplegic homolog 3 [KO:K23605]
109545112  5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
109535983  5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
109539842  uncharacterized protein LOC109539842 isoform X1 [KO:K07200]
109537697  serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
125503107  serine/threonine-protein kinase NLK-like [KO:K04468] [EC:2.7.11.24]
109546228  S-phase kinase-associated protein 2 [KO:K03875]
109535502  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109534501  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
109538246  ubiquitin carboxyl-terminal hydrolase 7 isoform X1 [KO:K11838] [EC:3.4.19.12]
109542184  stress-activated protein kinase JNK isoform X1 [KO:K04440] [EC:2.7.11.24]
125503343  stress-activated protein kinase JNK-like [KO:K04440] [EC:2.7.11.24]
109535797  bombyxin B-9 [KO:K04526]
109538758  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109540864  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109542293  3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
109540103  inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K07209] [EC:2.7.11.10]
109542185  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
109547011  RAC serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109540202  forkhead box protein O isoform X1 [KO:K09408]
109545639  homer protein homolog 2 isoform X1 [KO:K15010]
109536911  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
109536124  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
109538190  growth factor receptor-bound protein 2 [KO:K04364]
109537782  protein son of sevenless [KO:K03099]
109539276  ras-like protein 1 [KO:K07827]
109543674  raf homolog serine/threonine-protein kinase Raf [KO:K04365] [EC:2.7.11.1]
109540984  dual specificity mitogen-activated protein kinase kinase dSOR1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109535163  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125504664  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
109540885  mitogen-activated protein kinase p38b [KO:K04441] [EC:2.7.11.24]
109538506  cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
109536248  protein arginine N-methyltransferase 1-B [KO:K11434] [EC:2.1.1.319]
109540390  fork head domain transcription factor slp2 [KO:K09385]
109540399  fork head domain transcription factor slp2 [KO:K09385]
109544992  G2/mitotic-specific cyclin-B [KO:K21770]
109540321  G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
109541632  G1/S-specific cyclin-D2 [KO:K10151]
109536032  serine/threonine-protein kinase polo [KO:K06631] [EC:2.7.11.21]
109541525  serine/threonine-protein kinase PLK4 isoform X1 [KO:K08863] [EC:2.7.11.21]
109534077  uncharacterized protein LOC109534077 isoform X1 [KO:K04402]
109541093  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 isoform X1 [KO:K15464]
109534811  autophagy protein 12-like [KO:K08336]
109540010  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
109540718  catalase [KO:K03781] [EC:1.11.1.6]
109540720  catalase [KO:K03781] [EC:1.11.1.6]
109542104  catalase isoform X1 [KO:K03781] [EC:1.11.1.6]
109538109  catalase [KO:K03781] [EC:1.11.1.6]
109536658  superoxide dismutase [Mn] 1, mitochondrial [KO:K04564] [EC:1.15.1.1]
109546392  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
109533666  phosphoenolpyruvate carboxykinase [GTP] isoform X3 [KO:K01596] [EC:4.1.1.32]
109534522  F-box only protein 25 [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
dpa00010  Glycolysis / Gluconeogenesis
dpa00020  Citrate cycle (TCA cycle)
dpa00190  Oxidative phosphorylation
dpa04120  Ubiquitin mediated proteolysis
dpa04140  Autophagy - animal
dpa04350  TGF-beta signaling pathway
KO pathway
ko04068   
LinkDB

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