Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation

  • J Cell Biol. 2003 Sep 1;162(5):899-908. doi: 10.1083/jcb.200303158.
Lilia Topol  1 ,  Xueyuan Jiang ,  Hosoon Choi ,  Lisa Garrett-Beal ,  Peter J Carolan ,  Yingzi Yang
Affiliations
  • 1. Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
PMID: 12952940 DOI: 10.1083/jcb.200303158
Abstract

Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Wnt as it does not signal by stabilizing beta-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Wnt pathway by promoting the degradation of beta-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and beta-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.