Wnt-induced proteolytic targeting

Abstract

Misregulation of the Wnt pathway is a common route to cancer, including primary breast cancers. In this issue of Genes & Development, Miranda-Carboni and colleagues (pp. 3121-3134) demonstrate that the cyclin-dependent kinase inhibitor p27Kip1 is ubiquitylated for proteasomal degradation in Wnt10b-induced mammary tumors exclusively by the Cul4A E3 ligase, which is strongly induced by Wnt signaling. The discovery of a new Wnt-induced proteolytic targeting system has important implications for the mechanism of Wnt-initiated tumorigenesis. © 2008 by Cold Spring Harbor Laboratory Press.