Targeted degradation of beta-catenin by chimeric F-box fusion proteins.

Adenomatous polyposis coli (APC) tumor suppressor protein, together with Axin and glycogen synthase kinase 3beta (GSK-3beta), forms a Wnt-regulated signaling complex that mediates phosphorylation-dependent degradation of cytoplasmic beta-catenin by ubiquitin-dependent proteolysis. Degradation of phosphorylated beta-catenin is initiated by interaction through the WD40-repeat of a F-box protein beta-TrCP, a component of ...
SCF ubiquitin ligase complex. Mutations in APC, Axin, and beta-catenin that prevent down-regulation of cytoplasmic beta-catenin are found in various types of cancers. In the search for efficient treatment and prevention of malignancies associated with increased levels of cytoplasmic beta-catenin, we created chimeric F-box fusion proteins by replacing the WD40-repeat of beta-TrCP with the beta-catenin-binding domains of Tcf4 and E-cadherin. Expression of chimeric F-box fusion proteins successfully promotes degradation of beta-catenin independently of GSK-3beta-mediated phosphorylation. More importantly, this degradation does not require intact APC protein (pAPC).
Mesh Terms:
Adenomatous Polyposis Coli Protein, Cell Line, Cell Line, Tumor, Cytoskeletal Proteins, Down-Regulation, F-Box Proteins, Humans, Mutation, Recombinant Fusion Proteins, S-Phase Kinase-Associated Proteins, Trans-Activators, beta Catenin, beta-Transducin Repeat-Containing Proteins
Biochem. Biophys. Res. Commun.
Date: Jan. 23, 2004
Download Curated Data For This Publication
138490
Switch View:
  • Interactions 2
  • PTM Genes 1