COMPARATIVE CELL BASED FUNCTIONAL ANALYSIS OF KEY WNT/BETA-CATENIN PATHWAY GENES AND GENE MUTATIONS

The Wnt/Beta-catenin signaling pathway has many roles including regulation of developmental pathways, cell proliferation, and homeostasis of adult tissues. Wnt/Beta-catenin signaling activity depends on the stability and localization of Beta-catenin in the cell. In the absence of a Wnt-signal, Beta-catenin, which plays an integral role as a cell adhesion adapter protein and as a transcriptional coregulator, is phosphorylated by GSK3 Beta; in a complex with APC, AXIN, and CK1. Phosphorylation promotes ubiquitination of Beta-catenin and subsequent proteasomal degradation. When a Wnt-ligand binds to a Frizzled receptor, a signaling cascade displaces GSK3 Beta from its complex with Beta-catenin allowing Beta-catenin protein to accumulate and translocate to the nucleus. In the nucleus, Beta-catenin activates transcription of its target genes by binding TCF/LEF transcription factors. Aberrant Wnt/Beta-catenin signaling activity leads to misregulation of proliferation and metabolic pathways and has been linked to a number of diseases.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2012

Author dc:creator

• Manring, Heather Renee

• Beta-catenin

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/37663

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/37663