Regulation of Wnt/B-catenin Signaling by Small Molecule Compounds (Homo sapiens)

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1Gene TranscriptionFZD antibodiesTCF4FZDICG-001XAV939Glucocorticoids1a,25-(OH)2D3 CK1eiCRT14LEF1PyrviniumAXIN1FZD7SFRP4DVL2PRK222-815PRK115-584iCRT3FZD8LRPMBOATTNKSPRK118-744CK1aIC261WNTCGP049090RetinoidsCTNNB1DKK3iCRT5APCNC043IWP-2PRK118-310GSK3BNSC668036WNTUbV3NterWNT antibodiesDVL PDZ DomainsCTNNB1


Description

The Wnt/B-catenin pathway begins with Wnt family activation by MBOAT that allows Wnt proteins to translocate out of a cell and bind to FZD and LRP to form a complex. This complex stimulates B-catenin to bind to the TF/LEF complex to regulate gene expression in the cell. Regulation of this pathway takes place at different levels. The Wnt signaling can be inhibited by DKK3, FZD7, SFRP4, FZD8, V3Nter, and Wnt antibodies or FZD antibodies that inhibit FZD and do not allow formation of FZD/LRP/Wnt complex. Another level of regulation is the destruction complex (TNKS/AXIN/GSK3B/APC/CK1a/CK1e) that is regulated by XAV939, DVL, IC261, and Pyrvinium to catalyze the breakdown of B-catenin, inhibiting its binding to the TCF/LEF complex. Several substances including retinoids, glucocorticoids, and ICG-001 inhibit the TCF/LEF complex to stop Wnt/B-catenin signaling pathways from promoting gene transcription. This pathway is based on figure 4 from White et al.


Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

Quality Tags

Ontology Terms

 

Bibliography

  1. White BD, Chien AJ, Dawson DW; ''Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers.''; Gastroenterology, 2012 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
107145view14:23, 17 September 2019MaintBotChEBI identifier normalization
106496view21:44, 4 September 2019KhanspersModified description
105519view06:55, 8 August 2019KhanspersModified description
94746view15:14, 5 October 2017Mkutmonfix unconnected line
93253view09:18, 9 August 2017DeSlRemoved comment for node NC043
93252view09:17, 9 August 2017DeSlChanged ID of NC043 from INCHI to CAS.
93245view11:40, 8 August 2017DeSlChanged ID of 1a,25-(OH)2D3 to more stereospeific one; added 2 metabolite IDs which were previously not found.
93087view13:32, 28 July 2017DeSlChnaged all pubchem substance IDs to more stereospecified IDs
90182view18:19, 21 October 2016Khanspersfixed unconnected
90083view05:35, 13 October 2016KhanspersModified title
90082view05:34, 13 October 2016Khansperscleanup
88608view22:50, 11 August 2016AAR&CoOntology Term : 'gastrointestinal carcinoma' added !
88607view22:37, 11 August 2016AAR&CoPeriodical save, work in progress
88606view22:17, 11 August 2016AAR&CoPeriodical save, work in progress
87635view08:54, 25 July 2016LindarieswijkOntology Term : 'altered Wnt signaling pathway' added !
85938view18:54, 21 June 2016AAR&CoAdjust Interactions
85937view18:51, 21 June 2016AAR&CoAdjust Interactions to Wnt
85935view18:35, 21 June 2016AAR&CoFixed Unconnected Lines
85934view18:32, 21 June 2016AAR&CoModified description
85873view15:14, 19 June 2016AAR&CoModified description
85872view15:05, 19 June 2016AAR&CoNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1a,25-(OH)2D3 Metabolite5280453 (PubChem-compound)
APCGeneProductENSG00000134982 (Ensembl)
AXIN1GeneProductENSG00000103126 (Ensembl)
CGP049090MetaboliteCHEBI:3556 (ChEBI)
CK1aGeneProductENSG00000113712 (Ensembl)
CK1eGeneProductQ5R2U3 (Uniprot-TrEMBL)
CTNNB1GeneProductENSG00000168036 (Ensembl)
DKK3GeneProductENSG00000050165 (Ensembl)
DVL2GeneProductENSG00000004975 (Ensembl)
FZD7GeneProductENSG00000155760 (Ensembl)
FZD8GeneProductENSG00000177283 (Ensembl)
FZDGeneProductFZD1 (HGNC) FZD Not Specified
GSK3BGeneProductENSG00000082701 (Ensembl)
GlucocorticoidsMetaboliteCHEBI:24261 (ChEBI)
IC261MetaboliteCHEBI:92168 (ChEBI)
ICG-001Metabolite11238147 (PubChem-compound)
IWP-2Metabolite2155128 (PubChem-compound)
LEF1GeneProductENSG00000138795 (Ensembl)
LRPGeneProductENSG00000123384 (Ensembl) LRP Not Specified
MBOATGeneProductENSG00000172197 (Ensembl) MBOAT Family
NC043Metabolite1053172-87-4 (CAS)
NSC668036Metabolite338019 (Chemspider)
PRK115-584MetaboliteIdentifier Not Found
PRK118-310MetaboliteIdentifier Not Found
PRK118-744MetaboliteIdentifier Not Found
PRK222-815MetaboliteIdentifier Not Found
PyrviniumMetaboliteCHEBI:8687 (ChEBI)
RetinoidsMetaboliteCHEBI:26537 (ChEBI)
SFRP4GeneProductENSG00000106483 (Ensembl)
TCF4GeneProductENSG00000196628 (Ensembl)
TNKSGeneProductENSG00000173273 (Ensembl)
WNTGeneProductENSG00000125084 (Ensembl) Wnt Not Specified
XAV939MetaboliteCHEBI:62878 (ChEBI)
iCRT14Metabolite5967294 (PubChem-compound)
iCRT3Metabolite6622273 (PubChem-compound)
iCRT5Metabolite71749442 (PubChem-compound)

Annotated Interactions

No annotated interactions

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