Reaction heterodimer_association e_re527 map

LEF1_TCF3_4*@Nucleus map + _beta_-Catenin*@Cytoplasm map LEF1_TCF3_4*:​_beta_-Catenin*@Nucleus map

Reaction regulators:

  1. GTP:​RAC1@Cytoplasm map

-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.


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