beta-catenin-TCF complex assembly

Definition

Target type: biologicalprocess

The aggregation, arrangement and bonding together of a set of components to form a beta-catenin-TCF complex. [GO_REF:0000079, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:18936100]

The assembly of the beta-catenin-TCF complex is a crucial step in the Wnt signaling pathway, a highly conserved signaling cascade that plays fundamental roles in development, tissue homeostasis, and disease. Here's a detailed description of the process:

1. **Wnt Ligand Binding and Receptor Activation:** The process begins with the binding of Wnt proteins, a family of secreted signaling molecules, to their cognate receptors, Frizzled (Fzd) and LRP5/6. This binding event triggers a cascade of intracellular events.

2. **Dishevelled (Dsh) Activation:** Upon Wnt binding, Fzd activates Dishevelled (Dsh) protein, a cytoplasmic signaling molecule. Dsh acts as a scaffold protein, bringing together various components of the Wnt pathway.

3. **Axin/APC/GSK3β Complex Disassembly:** In the absence of Wnt signaling, a destruction complex consisting of Axin, adenomatous polyposis coli (APC), and glycogen synthase kinase 3 beta (GSK3β) is assembled. This complex targets beta-catenin for phosphorylation, marking it for degradation by the proteasome. However, Wnt signaling leads to the phosphorylation of LRP5/6 by Dsh, which promotes the recruitment of Axin to the receptor complex. This event sequesters Axin away from the destruction complex, leading to its disassembly.

4. **Beta-Catenin Stabilization and Nuclear Translocation:** With the destruction complex disassembled, beta-catenin escapes phosphorylation and degradation. It accumulates in the cytoplasm and subsequently translocates into the nucleus.

5. **Beta-Catenin-TCF Complex Formation:** Inside the nucleus, beta-catenin interacts with members of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors. These factors normally repress gene expression, but upon binding beta-catenin, they undergo a conformational change, converting them into transcriptional activators.

6. **Target Gene Transcription:** The beta-catenin-TCF complex binds to specific DNA sequences in the promoter regions of target genes, activating their transcription. These genes play vital roles in cell proliferation, differentiation, cell fate determination, and other developmental processes.

In summary, the assembly of the beta-catenin-TCF complex is a tightly regulated process that depends on the intricate interplay of multiple proteins and signaling events. This complex acts as a key transcriptional activator, driving the expression of genes crucial for various biological processes. Dysregulation of this pathway is linked to a wide range of developmental defects and cancers.'
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Proteins (2)

Compounds (1)