transcription factor 4
HUGO:TCF4 HGNC:11634 ENTREZ:6925 UNIPROT:P15884 GENECARDS:TCF4 REACTOME:57613 KEGG:6925 ATLASONC:GC_TCF4 WIKI:TCF4
lymphoid enhancer-binding factor 1
HUGO:LEF1 HGNC:6551 ENTREZ:51176 UNIPROT:Q9UJU2 GENECARDS:LEF1 KEGG:51176 ATLASONC:GC_LEF1 WIKI:LEF1
transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)
HUGO:TCF3 HGNC:11633 ENTREZ:6929 UNIPROT:P15923 GENECARDS:TCF3 REACTOME:65901 KEGG:6929 ATLASONC:E2A WIKI:TCF3
e_re527( EMT ):
-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
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)
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.
e_re620( EMT ):
The size of the LEF/TCF family is small: approximately 4 members in vertebrates.
The LEF/TCF family exhibits extensive patterns of alternative splicing, alternative promoter usage and activities of both repression and activation.
All LEF/TCFs bind b-catenin.
In compartment: Nucleus
Participates in complexes:
In compartment: Nucleus
Participates in reactions:
As Reactant or Product:
- LEF1_TCF3_4*@Nucleus → TCF3@Nucleus
- LEF1_TCF3_4*@Nucleus + _beta_-Catenin*@Cytoplasm → LEF1_TCF3_4*:_beta_-Catenin*@Nucleus
- LEF1_TCF3_4*@Nucleus → LEF1@Nucleus
- LEF1_TCF3_4*@Nucleus → TCF4@Nucleus