TCF4

Protein TCF4

Identifiers
transcription factor 4
HUGO:TCF4, HGNC:11634, ENTREZ:6925, UNIPROT:P15884, GENECARDS:GC18M052889
HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / ADHERENS_JUNCTIONS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL

References
PMID:15082531
The activation of MP3K7(TAK1) by TAB1 activates NLK. the TAK1???NLK MAPK pathway regulates Wnt signaling by phosphorylating TCF in mammalian cells.
The TAB1 protein is a specific partner of TAK1 and promotes TAK1 autophosphorylation.
Coexpression of TAK1 and TAB1 in mammalian cells activate HIPK2, that activate NLK. THe coexpression of NLK and HIPK2 induces the degradation of the c-Myb protein.
Degradation of c-Myb protein by Wnt-1 signal via the pathway involving TAK1, HIPK2, and NLK leads to G1 arrest.
PMID:10391247
TAK1 activation stimulates NLK activity and downregulates transcriptional activation mediated by beta-catenin and TCF.

TCF4@Nucleus

TCF4|pho@Nucleus

References
em_re1521( EMT Senescence ):
PMID:15082531
The activation of MP3K7(TAK1) by TAB1 activates NLK. the TAK1???NLK MAPK pathway regulates Wnt signaling by phosphorylating TCF in mammalian cells.
The TAB1 protein is a specific partner of TAK1 and promotes TAK1 autophosphorylation.
Coexpression of TAK1 and TAB1 in mammalian cells activate HIPK2, that activate NLK. THe coexpression of NLK and HIPK2 induces the degradation of the c-Myb protein.
Degradation of c-Myb protein by Wnt-1 signal via the pathway involving TAK1, HIPK2, and NLK leads to G1 arrest.
PMID:10391247
TAK1 activation stimulates NLK activity and downregulates transcriptional activation mediated by beta-catenin and TCF.
em_emtc_emtc_re527( EMT Senescence ):
PMID:19751508
PMID:22270359
PMID:16940750
-In the absence of Wnt ligands, b-catenin is phosphorylated by CK1 and GSK-3 in the context of a destruction complex with APC and Axin.
Phosphorylated b-catenin is consequently targeted for ubiquitination and degraded.
-In the presence of Wnt lignads, upon ligand binding, DVL1 (dishevelled) recruits the Axin-GSK-3 complex, resulting in the sequential phosphorylation of LRP6 by CK1 and GSK-3.
Phoshorylated LRP6 serves as a docking site for additional Axin-GSK-3 complex, resulting in the disassembly of the destruction complex.
Non phosphorylated and thus stabilized b-catenin translocates to the nucleus where it activates transcription of target genes together with LEF/TCFs
PMID:19020303
When Wnt binds its receptor, Frizzled, beta-catenin is released to translocate from the cytoplasm to the nucleus, where it forms a complex with TCF and/or LEF transcription factors and stimulates cyclin D1 gene transcription
(Beta-catenin/TCF)- mediated cyclin D1 gene transcription is further regulated by active Rac signaling, phosphorylation by protein kinase A (PKA)
PMID:15377999
Rac1-GTP augments nuclear accumulation of b-catenin and physical association of Rac1 with b-catenin and/or TCF-4 may facilitate this process.
This culminates in the amplification of b-catenin signaling activity, resulting in enhanced transcriptional activation of perhaps a specific subset of Wnt target genes important in cancer progression.
NLK phosphorylates TCF/LEF factors and inhibits the interaction of the beta-catenin???TCF complex with DNA.

Modifications:
In compartment: Nucleus

TCF4@Nucleus
TCF4|pho@Nucleus

Participates in complexes:
In compartment: Nucleus

Participates in reactions:
As Reactant or Product:

As Catalyser: