FOXO-mediated transcription of cell death genes (Homo sapiens)

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1-15, 17, 19...3, 9194, 11, 23191, 51, 5, 7, 20, 253, 94, 11, 2318, 21nucleoplasmcytosolNF-YFOXO1 CITED2NFYB FOXO3,FOXO4,(FOXO1)DDIT3CREBBP NFYB EP300 FOXO1 FOXO3 FASLG gene NFYA FOXO1,FOXO3,(FOXO4):FASLG geneFOXO3,FOXO4FOXO4 FOXO1 FOXO1 BBC3 genePINK1 geneNFYC FOXO4 FOXO3 PINK1 gene BCL6 geneBCL2L11 geneFOXO4 FOXO3 FOXO4 CITED2 geneFOXO1 FOXO3 FOXO3 NF-Y:CREBBP,EP300:BCL2L11 geneBCL2L11FASLG(1-281)CREBBP FASLG geneNFYC FOXO1,FOXO3,(FOXO4):NF-Y:CREBBP,EP300:BCL2L11 geneNFYB BBC3CITED2 gene FOXO3 EP300 CREBBP,EP300BCL6FOXO1 FOXO1 NFYA FOXO1,FOXO3:CITED2geneEP300 FOXO3,(FOXO1):BBC3geneFOXO1 STK11 geneNFYA FOXO3 FOXO3 FOXO1,FOXO3:PINK1geneFOXO3,FOXO4,(FOXO1):BCL6 geneFOXO1 NFYC FOXO3,(FOXO1)FOXO3 FOXO1,FOXO3FOXO4 CREBBP FOXO1 FOXO3 FOXO3 STK11 gene BCL6 gene FOXO3 BCL2L11 gene FOXO4 STK11BCL2L11 gene FOXO3,FOXO4:STK11geneFOXO4 BBC3 gene FOXO1,FOXO3,(FOXO4)PINK116


Description

FOXO transcription factors promote expression of several pro-apoptotic genes, such as FASLG (Brunet et al. 1999, Ciechomska et al. 2003, Chen et al. 2013, Li et al. 2015), PINK1 (Mei et al. 2009, Sengupta et al. 2011), BCL2L11 (BIM) (Gilley et al. 2003, Urbich et al. 2005, Chuang et al. 2007, Hughes et al. 2011, Chen et al. 2013, Wang et al. 2016), BCL6 (Tang et al. 2002, Fernandez de Mattos et al. 2004, Shore et al. 2006) and BBC3 (PUMA) (Dudgeon et al. 2010, Hughes et al. 2011, Liu et al. 2015, Wu et al. 2016, Liu et al. 2017, Fitzwalter et al. 2018). FOXO-mediated induction of cell death genes is important during development, for example during nervous system development, where FOXO promotes neuronal death upon NGF withdrawal (Gilley et al. 2003), and also contributes to the tumor-suppressive role of FOXO factors (Arimoto Ishida et al. 2004). FOXO1 transcriptional activity is implicated in the cell death of enteric nervous system (ENS) precursors. RET signaling, which activates PI3K/AKT signaling, leading to inhibition of FOXO mediated transcription, ensures survival of ENS precursors (Srinivasan et al. 2005).
Transcription of the STK11 (LKB1) gene, encoding Serine/threonine-protein kinase STK11 (also known as Liver kinase B1), which regulates diverse cellular processes, including apoptosis, is directly stimulated by FOXO3 and FOXO4 (Lutzner et al. 2012). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 9614657
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

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Bibliography

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  1. Ciechomska I, Pyrzynska B, Kazmierczak P, Kaminska B.; ''Inhibition of Akt kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells.''; PubMed Europe PMC Scholia
  2. Urbich C, Knau A, Fichtlscherer S, Walter DH, Brühl T, Potente M, Hofmann WK, de Vos S, Zeiher AM, Dimmeler S.; ''FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells.''; PubMed Europe PMC Scholia
  3. Dudgeon C, Wang P, Sun X, Peng R, Sun Q, Yu J, Zhang L.; ''PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01.''; PubMed Europe PMC Scholia
  4. Tang TT, Dowbenko D, Jackson A, Toney L, Lewin DA, Dent AL, Lasky LA.; ''The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor.''; PubMed Europe PMC Scholia
  5. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME.; ''Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.''; PubMed Europe PMC Scholia
  6. Chuang PY, Yu Q, Fang W, Uribarri J, He JC.; ''Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor.''; PubMed Europe PMC Scholia
  7. Chen L, Tang Y, Wang J, Yan Z, Xu R.; ''miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4.''; PubMed Europe PMC Scholia
  8. Mei Y, Zhang Y, Yamamoto K, Xie W, Mak TW, You H.; ''FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation.''; PubMed Europe PMC Scholia
  9. Fitzwalter BE, Towers CG, Sullivan KD, Andrysik Z, Hoh M, Ludwig M, O'Prey J, Ryan KM, Espinosa JM, Morgan MJ, Thorburn A.; ''Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover.''; PubMed Europe PMC Scholia
  10. Gilley J, Coffer PJ, Ham J.; ''FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons.''; PubMed Europe PMC Scholia
  11. Fernández de Mattos S, Essafi A, Soeiro I, Pietersen AM, Birkenkamp KU, Edwards CS, Martino A, Nelson BH, Francis JM, Jones MC, Brosens JJ, Coffer PJ, Lam EW.; ''FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism.''; PubMed Europe PMC Scholia
  12. Wang W, Zhou PH, Hu W.; ''Overexpression of FOXO4 induces apoptosis of clear-cell renal carcinoma cells through downregulation of Bim.''; PubMed Europe PMC Scholia
  13. Liu ZQ, Shen M, Wu WJ, Li BJ, Weng QN, Li M, Liu HL.; ''Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress.''; PubMed Europe PMC Scholia
  14. Liu T, Chen X, Li T, Li X, Lyu Y, Fan X, Zhang P, Zeng W.; ''Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway.''; PubMed Europe PMC Scholia
  15. Sengupta A, Molkentin JD, Paik JH, DePinho RA, Yutzey KE.; ''FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress.''; PubMed Europe PMC Scholia
  16. Shioda T, Fenner MH, Isselbacher KJ.; ''msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation.''; PubMed Europe PMC Scholia
  17. Hughes R, Kristiansen M, Lassot I, Desagher S, Mantovani R, Ham J.; ''NF-Y is essential for expression of the proapoptotic bim gene in sympathetic neurons.''; PubMed Europe PMC Scholia
  18. Bakker WJ, Harris IS, Mak TW.; ''FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2.''; PubMed Europe PMC Scholia
  19. Lützner N, De-Castro Arce J, Rösl F.; ''Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO transcription factors.''; PubMed Europe PMC Scholia
  20. Li J, Hu L, Tian C, Lu F, Wu J, Liu L.; ''microRNA-150 promotes cervical cancer cell growth and survival by targeting FOXO4.''; PubMed Europe PMC Scholia
  21. Wang X, Lockhart SM, Rathjen T, Albadawi H, Sørensen D, O'Neill BT, Dwivedi N, Preil SR, Beck HC, Dunwoodie SL, Watkins MT, Rasmussen LM, Rask-Madsen C.; ''Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells.''; PubMed Europe PMC Scholia
  22. Srinivasan S, Anitha M, Mwangi S, Heuckeroth RO.; ''Enteric neuroblasts require the phosphatidylinositol 3-kinase/Akt/Forkhead pathway for GDNF-stimulated survival.''; PubMed Europe PMC Scholia
  23. Shore AM, White PC, Hui RC, Essafi A, Lam EW, Rowe M, Brennan P.; ''Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A.''; PubMed Europe PMC Scholia
  24. Wu B, Guo B, Kang J, Deng X, Fan Y, Zhang X, Ai K.; ''Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-β-induced tumor formation.''; PubMed Europe PMC Scholia
  25. Arimoto-Ishida E, Ohmichi M, Mabuchi S, Takahashi T, Ohshima C, Hayakawa J, Kimura A, Takahashi K, Nishio Y, Sakata M, Kurachi H, Tasaka K, Murata Y.; ''Inhibition of phosphorylation of a forkhead transcription factor sensitizes human ovarian cancer cells to cisplatin.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
114779view16:27, 25 January 2021ReactomeTeamReactome version 75
113224view11:29, 2 November 2020ReactomeTeamReactome version 74
112800view17:53, 9 October 2020DeSlOntology Term : 'forkhead class O signaling pathway' added !
112750view16:15, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
BBC3 gene ProteinENSG00000105327 (Ensembl)
BBC3 geneGeneProductENSG00000105327 (Ensembl)
BBC3ProteinQ9BXH1 (Uniprot-TrEMBL)
BCL2L11 gene ProteinENSG00000153094 (Ensembl)
BCL2L11 geneGeneProductENSG00000153094 (Ensembl)
BCL2L11ProteinO43521 (Uniprot-TrEMBL)
BCL6 gene ProteinENSG00000113916 (Ensembl)
BCL6 geneGeneProductENSG00000113916 (Ensembl)
BCL6ProteinP41182 (Uniprot-TrEMBL)
CITED2 gene ProteinENSG00000164442 (Ensembl)
CITED2 geneGeneProductENSG00000164442 (Ensembl)
CITED2ProteinQ99967 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CREBBP,EP300ComplexR-HSA-1027362 (Reactome)
DDIT3ProteinP35638 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
FASLG gene ProteinENSG00000117560 (Ensembl)
FASLG geneGeneProductENSG00000117560 (Ensembl)
FASLG(1-281)ProteinP48023 (Uniprot-TrEMBL)
FOXO1 ProteinQ12778 (Uniprot-TrEMBL)
FOXO1,FOXO3,(FOXO4):FASLG geneComplexR-HSA-9614664 (Reactome)
FOXO1,FOXO3,(FOXO4):NF-Y:CREBBP,EP300:BCL2L11 geneComplexR-HSA-9622581 (Reactome)
FOXO1,FOXO3,(FOXO4)ComplexR-HSA-9620827 (Reactome)
FOXO1,FOXO3:CITED2 geneComplexR-HSA-9621111 (Reactome)
FOXO1,FOXO3:PINK1 geneComplexR-HSA-9621278 (Reactome)
FOXO1,FOXO3ComplexR-HSA-9614686 (Reactome)
FOXO3 ProteinO43524 (Uniprot-TrEMBL)
FOXO3,(FOXO1):BBC3 geneComplexR-HSA-9622685 (Reactome)
FOXO3,(FOXO1)ComplexR-HSA-9622696 (Reactome)
FOXO3,FOXO4,(FOXO1):BCL6 geneComplexR-HSA-9622662 (Reactome)
FOXO3,FOXO4,(FOXO1)ComplexR-HSA-9617860 (Reactome)
FOXO3,FOXO4:STK11 geneComplexR-HSA-9625394 (Reactome)
FOXO3,FOXO4ComplexR-HSA-9623421 (Reactome)
FOXO4 ProteinP98177 (Uniprot-TrEMBL)
NF-Y:CREBBP,EP300:BCL2L11 geneComplexR-HSA-9622566 (Reactome)
NF-YComplexR-HSA-381204 (Reactome) NF-Y is a ubiquitous heterotrimeric transcription factor comprising subunits NF-Y A, NF-Y B, and NF-Y C. It binds the sequence CCAAT.
NFYA ProteinP23511 (Uniprot-TrEMBL)
NFYB ProteinP25208 (Uniprot-TrEMBL)
NFYC ProteinQ13952 (Uniprot-TrEMBL)
PINK1 gene ProteinENSG00000158828 (Ensembl)
PINK1 geneGeneProductENSG00000158828 (Ensembl)
PINK1ProteinQ9BXM7 (Uniprot-TrEMBL)
STK11 gene ProteinENSG00000118046 (Ensembl)
STK11 geneGeneProductENSG00000118046 (Ensembl)
STK11ProteinQ15831 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
BBC3 geneR-HSA-9622667 (Reactome)
BBC3 geneR-HSA-9622668 (Reactome)
BBC3ArrowR-HSA-9622667 (Reactome)
BCL2L11 geneR-HSA-9622572 (Reactome)
BCL2L11 geneR-HSA-9622604 (Reactome)
BCL2L11ArrowR-HSA-9622604 (Reactome)
BCL6 geneR-HSA-9622627 (Reactome)
BCL6 geneR-HSA-9622630 (Reactome)
BCL6ArrowR-HSA-9622627 (Reactome)
CITED2 geneR-HSA-9621116 (Reactome)
CITED2 geneR-HSA-9621242 (Reactome)
CITED2ArrowR-HSA-9621242 (Reactome)
CREBBP,EP300R-HSA-9622572 (Reactome)
DDIT3ArrowR-HSA-9622604 (Reactome)
DDIT3ArrowR-HSA-9622667 (Reactome)
FASLG geneR-HSA-9614662 (Reactome)
FASLG geneR-HSA-9614669 (Reactome)
FASLG(1-281)ArrowR-HSA-9614669 (Reactome)
FOXO1,FOXO3,(FOXO4):FASLG geneArrowR-HSA-9614662 (Reactome)
FOXO1,FOXO3,(FOXO4):FASLG geneArrowR-HSA-9614669 (Reactome)
FOXO1,FOXO3,(FOXO4):NF-Y:CREBBP,EP300:BCL2L11 geneArrowR-HSA-9622579 (Reactome)
FOXO1,FOXO3,(FOXO4):NF-Y:CREBBP,EP300:BCL2L11 geneArrowR-HSA-9622604 (Reactome)
FOXO1,FOXO3,(FOXO4)R-HSA-9614662 (Reactome)
FOXO1,FOXO3,(FOXO4)R-HSA-9622579 (Reactome)
FOXO1,FOXO3:CITED2 geneArrowR-HSA-9621116 (Reactome)
FOXO1,FOXO3:CITED2 geneArrowR-HSA-9621242 (Reactome)
FOXO1,FOXO3:PINK1 geneArrowR-HSA-9621270 (Reactome)
FOXO1,FOXO3:PINK1 geneArrowR-HSA-9621289 (Reactome)
FOXO1,FOXO3R-HSA-9621116 (Reactome)
FOXO1,FOXO3R-HSA-9621270 (Reactome)
FOXO3,(FOXO1):BBC3 geneArrowR-HSA-9622667 (Reactome)
FOXO3,(FOXO1):BBC3 geneArrowR-HSA-9622668 (Reactome)
FOXO3,(FOXO1)R-HSA-9622668 (Reactome)
FOXO3,FOXO4,(FOXO1):BCL6 geneArrowR-HSA-9622627 (Reactome)
FOXO3,FOXO4,(FOXO1):BCL6 geneArrowR-HSA-9622630 (Reactome)
FOXO3,FOXO4,(FOXO1)R-HSA-9622630 (Reactome)
FOXO3,FOXO4:STK11 geneArrowR-HSA-9625375 (Reactome)
FOXO3,FOXO4:STK11 geneArrowR-HSA-9625378 (Reactome)
FOXO3,FOXO4R-HSA-9625375 (Reactome)
NF-Y:CREBBP,EP300:BCL2L11 geneArrowR-HSA-9622572 (Reactome)
NF-Y:CREBBP,EP300:BCL2L11 geneR-HSA-9622579 (Reactome)
NF-YR-HSA-9622572 (Reactome)
PINK1 geneR-HSA-9621270 (Reactome)
PINK1 geneR-HSA-9621289 (Reactome)
PINK1ArrowR-HSA-9621289 (Reactome)
R-HSA-9614662 (Reactome) Unphosphorylated FOXO1 (Ciechomska et al. 2003) and FOXO3 (Brunet et al. 1999), and possibly FOXO4, can bind to three Forkhead-responsive elements in the promoter of the FASLG gene. The FASLG gene encodes FAS ligand (also known as TNFSF6 or CD95-L), a cytokine that binds the FAS receptor (TNFRSF6) and triggers extrinsic apoptosis pathway. AKT-mediated phosphorylation of FOXO3 prevents binding of FOXO3 to the FASLG promoter (Brunet et al. 1999).
R-HSA-9614669 (Reactome) Binding of FOXO1 (Ciechomska et al. 2003) or FOXO3 (Brunet et al. 1999, Arimoto-Ishida et al. 2004) to the promoter of the FASLG gene directly stimulates FASLG transcription. FOXO4 stimulates FASLG gene expression, as microRNA-mediated inhibition of FOXO4 mRNA translation results in decreased levels of FASLG. Direct binding of FOXO4 to the FASLG gene promoter, however, has not been demonstrated (Chen et al. 2013, Li et al. 2015). FASLG (Fas ligand) is a cytokine that belongs to the family of tumor necrosis factors involved in extrinsic apoptotic signaling. In ovarian cancer, cisplatin resistance may be partially attributable to inhibition of FOXO3-mediated induction of FASLG by PI3K/AKT signaling cascade (Arimoto-Ishida et al. 2004).
R-HSA-9621116 (Reactome) Both FOXO1 (Sengupta et al. 2011) and FOXO3 (Bakker, van Dijk et al. 2007, Bakker, Harris and Mak 2007) can bind forkhead box elements in the promoter region of the CITED2 gene. The involvement of specific FOXO family members (Sengupta et al. 2011), specific forkhead box elements (Bakker, Harris and Mak 2007) and required co-factors, such as STAT5 (Bakker, van Dijk et al. 2007), depends on the cell type and the trigger of FOXO activity.
R-HSA-9621242 (Reactome) FOXO1 and FOXO3 directly stimulate transcription of the CITED2 gene, encoding a transcription factor CITED2 (also known as MRG1). In erythroid cell progenitors, FOXO3-mediated induction of CITED2 transcription may require erythropoietin-induced formation of the complex of FOXO3 and STAT5 (Bakker et al. 2007). FOXO3-mediated induction of CITED2 in response to hypoxic stress prevents HIF1-induced apoptosis (Bakker et al. 2007). Upregulation of CITED2, mediated by FOXO1 and/or FOXO3, enables survival of cardiomyocytes under oxidative stress (Sengupta et al. 2011). Vascular insulin resistance in type 2 diabetes leads to FOXO1-mediated upregulation of CITED2, which interferes with HIF-induced angiogenesis (Wang et al. 2016).
R-HSA-9621270 (Reactome) FOXO1 (Sengupta et al. 2011) and FOXO3 (Mei et al. 2009, Sengupta et al. 2011) bind forkhead box elements in the promoter region of the PINK1 gene.
R-HSA-9621289 (Reactome) FOXO1 (Sengupta et al. 2011) and FOXO3 (Mei et al. 2009, Sengupta et al. 2011) stimulate PINK1 gene transcription in both human (Mei et al. 2009) and mouse cells. FOXO3-mediated induction of PINK1 plays an important role in the survival of lymphocytes (Mei et al. 2009).
R-HSA-9622572 (Reactome) Based on studies in rat neurons, the NF-Y transcription factor complex (composed of NFYA, NFYB and NFYC) and histone acetyltransferases EP300 (p300) and/or CREBBP (CBP) constitutively bind to evolutionarily conserved sites in the promoter of the BCL2L11 (BIM) gene (Hughes et al. 2011).
R-HSA-9622579 (Reactome) Based on studies in rat neurons, in the absence of PI3K/AKT signaling, as happens under conditions of NGF withdrawal, for example, FOXO transcription factors, FOXO3, FOXO1 and probably also FOXO4 bind evolutionarily conserved forkhead box elements in the promoter of the BCL2L11 (BIM) gene (Gilley et al. 2003) and co-immunoprecipitate with the BCL2L11 promoter-bound NF-Y complex (Hughes et al. 2011).
R-HSA-9622604 (Reactome) BCL2L11 (BIM) gene transcription is stimulated by FOXO transcription factors FOXO1 (Gilley et al. 2003), FOXO3 (Gilley et al. 2003, Hughes et al. 2011) and FOXO4 (Urbich et al. 2005, Chuang et al. 2007, Chen et al. 2013, Wang et al. 2016), the NF-Y transcription factor complex (Hughes et al. 2011), and histone acetyltransferases CREBBP and/or EP300 (Hughes et al. 2011). Direct transcriptional regulation of BCL2L11 gene has not been demonstrated for FOXO4. FOXO-mediated upregulation of the pro-apoptotic BCL2L11 plays an important role in NGF withdrawal-induced death of sympathetic neurons (Gilley et al. 2003, Hughes et al. 2011).
FOXO-mediated upregulation of BCL2L11 gene transcription is positively regulated by DDIT3 (CHOP) through an unknown mechanism that may involve binding of DDIT3 to FOXO3 (Ghosh et al. 2012).
R-HSA-9622627 (Reactome) Transcription of the BCL6 gene, encoding a pro-apoptotic transcriptional repressor, is directly stimulated by FOXO3 (Fernandez de Mattos et al. 2004) and FOXO4 (AFX) (Tang et al. 2002). FOXO1 stimulates BCL6 gene transcription (Shore et al. 2006), but direct binding of FOXO1 to the BCL6 gene promoter has not been demonstrated.
R-HSA-9622630 (Reactome) FOXO3 (Fernandez de Mattos et al. 2004), FOXO4 (AFX) (Tang et al. 2002), and probably FOXO1 (Shore et al. 2006) bind to forkhead box elements in the promoter of the BCL6 gene.
R-HSA-9622667 (Reactome) Transcription of the pro-apoptotic BBC3 (PUMA) gene is directly stimulated by FOXO3 (Dudgeon et al. 2010, Fitzwalter et al. 2018). FOXO1 upregulates BBC3 transcription (Hughes et al. 2011, Liu et al. 2015, Wu et al. 2016, Liu et al. 2017), but direct binding to the BBC3 gene locus has not been demonstrated.
FOXO-mediated upregulation of BBC3 gene transcription is positively regulated by DDIT3 (CHOP) through an unknown mechanism. DDIT3 is able to bind FOXO3, but the physiological role and context of this protein complex is not known (Ghosh et al. 2012).
R-HSA-9622668 (Reactome) FOXO3 binds forkhead box elements in the first intron of the BBC3 (PUMA) gene (Dudgeon et al. 2010, Fitzwalter et al. 2018). As FOXO1 upregulates BBC3 transcription, it is probable that FOXO1 can also associate with forkhead box elements in the BBC3 gene locus.
R-HSA-9625375 (Reactome) FOXO3 and FOXO4 bind to forkhead box elements in the promoter region of the STK11 (LKB1) gene, encoding Serine/threonine-protein kinase STK11 (also known as Liver kinase B1). The promoter of the STK11 gene also possesses binding sites for transcription factors NF-Y and SP1. It is unclear if FOXO3 and FOXO4 cooperate with NF-Y and SP1 in the induction of STK11 transcription (Lutzner et al. 2012).
R-HSA-9625378 (Reactome) Transcription of the STK11 (LKB1) gene, encoding Serine/threonine-protein kinase STK11 (also known as Liver kinase B1) is directly stimulated by FOXO3 and FOXO4. It is unclear if FOXO3 and FOXO4 cooperate with NF-Y and SP1, which can also bind to the STK11 gene promoter, in the induction of STK11 transcription (Lutzner et al. 2012). STK11 regulates diverse cellular processes, including apoptosis (reviewed in Zhao and Xu 2014).
STK11 geneR-HSA-9625375 (Reactome)
STK11 geneR-HSA-9625378 (Reactome)
STK11ArrowR-HSA-9625378 (Reactome)
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