Characterization of a beta-Catenin-Associated Kinase
Abstract
Beta-catenin is an important regulator of cell-cell adhesion and embryonic development that associates with and regulates the function of the LEF/TCF family of transcription factors. Mutations of Beta-catenin and the tumor suppressor gene APC occur in human cancers but it is not known if and by what mechanism increased Beta-catenin causes cellular transformation. This study was the first to show a serine phosphorylation-dependent regulation of Beta-catenin ubiquitination and degradation. We went on to demonstrate that modest over-expression of Beta-catenin in a normal epithelial cell results in cellular transformation. These cells form colonies in soft agar, survive in suspension, and continue to proliferate at high cell density and following y-irradiation. Endogenous cytoplasmic beta-catenin levels and signaling activity were also found to oscillate during the cell cycle. Taken together, these data point to a role of beta-catenin in the regulation of the G1 to S phase transition and suspension induced apoptosis (anoikis). Additional results point to the important role played by two serine kinases (IKK and atypical PKC) in the normal phosphorylation and regulation of 3-catenin signaling activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA405220
Entities
People
- Keith Orford
- Stephen Byers
Organizations
- Georgetown University