Wnt-induced proteolytic targeting.
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 (3121-3134) demonstrate that the cyclin-dependent kinase inhibitor p27(Kip1) 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.
Jones
Katherine A
KA
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. jones@salk.edu
Kemp
Caroline R
CR
D000818:Animals; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
C114234:CUL4A protein, human; D044842:Cullin Proteins; D044786:S-Phase Kinase-Associated Proteins; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D046988:Proteasome Endopeptidase Complex