Item Details

title

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

author

Manring, Heather Renee

abstract

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.

subject

Beta-catenin

cancer

diabetes

Wnt

contributor

Antinozzi, Peter A (committee chair)

Miller, Lance (committee member)

Torti, Suzy (committee member)

Townsend, Alan (committee member)

Wilkinson, John (committee member)

date

2013-01-09T09:35:14Z (accessioned)

2015-01-09T09:30:09Z (available)

2012 (issued)

degree

Biochemistry and Molecular Biology (discipline)

embargo

2015-01-09 (terms)

identifier

http://hdl.handle.net/10339/37663 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation