Defining Components of the ßcatenin Destruction Complex and Exploring Its Regulation and Mechanisms of Action during Development

PLOS ONE, February 2012

22359584

David M. Roberts, Mira I. Pronobis, Kelly M. Alexandre, Gregory C. Rogers, John S. Poulton, Daniel E. Schneider, Kuo-Chen Jung, Daniel J. McKay, Mark Peifer

A subset of signaling pathways play exceptionally important roles in embryonic and post-embryonic development, and mis-regulation of these pathways occurs in most human cancers. One such pathway is the Wnt pathway. The primary mechanism keeping Wnt signaling off in the absence of ligand is regulated proteasomal destruction of the canonical Wnt effector ßcatenin (or its fly homolog Armadillo). A substantial body of evidence indicates that SCF(βTrCP) mediates βcat destruction, however, an essential role for Roc1 has not been demonstrated in this process, as would be predicted. In addition, other E3 ligases have also been proposed to destroy βcat, suggesting that βcat destruction may be regulated differently in different tissues.