Journal
JOURNAL OF CELL BIOLOGY
Volume 162, Issue 5, Pages 899-908Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200303158
Keywords
limb; chondrogenesis; cancer; Siah2; APC
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Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Writ 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 Writ 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.
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