Genes

CTNNB1

CTNNB1 is the gene which encodes the ß-catenin protein. ß-catenin is part of a complex of proteins that form adherens junctions, which are important for the establishment and maintenance of epithelial cell layers by regulating cell growth and adhesion between adjacent cells (Hartsock and Nelson 2008). ß-catenin is also part of the canonical Wnt signaling pathway (Figure 1). In the absence of Wnt signaling, glycogen synthase kinase-3 (GSK-3) phosphorylates ß-catenin, thereby targeting ß-catenin for degradation via the ubiquitin-proteasome system. When Wnt binds to its receptor, Frizzled, ß-catenin phosphorylation and ubiquitin-mediated degradation are blocked. ß-catenin is then free to translocate to the cell nucleus where it acts as a co-factor for the T-cell factor/lymphoid enhancing factor (TCF/LEF) transcription factors. The ß-catenin-TCF/LEF complex results in the activation of targets including c-MYC and Cyclin-D1 (for review, see Giles, van Es, and Clevers 2003).

Mutant CTNNB1 (ß-catenin) has been implicated in the pathogenesis of several cancers including melanoma, colorectal cancer, hepatocelluar carcinoma, and ovarian cancer (Giles, van Es, and Clevers 2003).

wnt-signaling.png

Figure 1.
Simplified schematic of the Wnt signaling pathway. In the absence of Wnt signaling, ß-catenin is phosphorylated by GSK-3, thereby resulting in poly-ubiquitination and degradation by the 20S proteasome system. When Wnt binds to its receptor, Frizzled, ß-catenin is stabilized. ß-catenin subsequently translocates to the nucleus, where it acts as a co-factor for the TCF/LEF family of transcription factors.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Jeff Sosman, M.D., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C.M., Sosman, J., Pao, W. 2015. CTNNB1. My Cancer Genome https://www.padiracinnovation.org/content/gene/ctnnb1/ (Updated December 2015)

Modified: December 4, 2015

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