2012 Group 5 Project

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2012 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8 | Group 9

Wnt/Beta-catenin Signalling Pathway



Normal Function

  • Wnt proteins encompass a network of secreted glycolipoproteins
  • Wnt signalling best known for playing a variety roles in embryogenesis, control of cellular proliferation and the resulting birth defects, cancers and other diseases arising from mutations in the pathway [1]
  • Beta-catenin commonly exists as a subunit making up the cadherin protein complex
  • Cadherin proteins play an integral role in the formation of adhesion junctions between cells
  • Beta-catenin also acts to help anchor the actin cytoskeleton within the cell
  • Beta-catenin plays a vital role in the Wnt signalling pathway by directly affecting the control of protein synthesis within the cell. The interaction of beta-catenin with the TCF/LEF family of transcription factors on the template DNA strand converts them from repressors to activators, triggering downstream transcription of Wnt target genes and synthesis of their encoded proteins. [2]
  • This interaction is reliant on an intracellular cascade which ultimately dictates the amount of Beta-catenin present in the cytoplasm which is then able to reach the nucleus and effect transcription.
  • In the absence of Wnt (“off state”), beta-catenin is targeted for proteasomal degradation. Intracellular Axin, GSK-3β (glycogen synthase kinase 3β) and APC (Adenomatous polyposis coli – coded for by the APC tumour suppressor gene) form a “destruction complex” leading to phosphorylation of β-catenin by the coordinated action of CK1 and GSK-3β and subsequent ubiquination. [3]
  • In the presence of Wnt (“on state”) an extracellular “Wnt signal” binds to a cell surface G-protein coupled receptor of the “Frizzled” (FRZ) family. This results in the activation (phosphorylation and poly-ubiquination) of proteins of the “Dishevelled” (DSH) family implicated in the inactivation of the “destruction complex” by the recruitment of GSK-3β away from the complex. With the complex now interrupted, an increased amount of beta-catenin is able to reach the nucleus where it can promote transcription of Wnt target genes. [4]
  • Low-density lipoprotein receptor-related protein (LRP) family functions as a transmembrane co-receptor for Frizzled. It functions to recruit axin to the membrane, leading to axin degradation upon the initiation of the Wnt signalling cascade and the dissociation of beta-catenin into the cytoplasm without degradation by the “destruction complex”. [5]
  • The Beta-catenin gene can be said to function as an oncogene given that the promotion of transcription of Wnt target genes by beta-catenin has been shown to be involved in the development of basal cell carcinoma, colorectal cancer and breast cancer. [6]

File:Overview of Wnt Beta-catenin Signalling.jpg [2]

Abnormal Function

File:Table 1. Human Diseases Associated with Mutations of the Wnt Signaling Components.png
Table 1. Human Diseases Associated with Mutations of the Wnt Signaling Components [7]


  • Frizzled receptor


  • Wnt
  • beta-catenin
  • Frizzled proteins

Glossary of Terms

Reference List

  1. <pubmed>17081971</pubmed>
  2. 2.0 2.1 <pubmed>19619488</pubmed>
  3. <pubmed>15084453</pubmed>
  4. <pubmed>19736321</pubmed>
  5. <pubmed>19279722</pubmed>
  6. <pubmed>18708403</pubmed>
  7. <pubmed>19619488</pubmed>

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