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.
MeSH terms
-
Adenomatous Polyposis Coli Protein / metabolism
-
Animals
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cell Line
-
Cell Line, Tumor
-
Culture Techniques
-
Cytoskeletal Proteins / metabolism*
-
DNA-Binding Proteins / metabolism
-
Embryo, Mammalian / anatomy & histology
-
Embryo, Mammalian / physiology
-
Embryonic Structures / metabolism
-
Enzyme Activation
-
Gene Expression Regulation
-
Genes, Reporter
-
Glycogen Synthase Kinase 3 / metabolism*
-
Humans
-
Mice
-
Mice, Transgenic
-
NFATC Transcription Factors
-
Nuclear Proteins / metabolism
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
Signal Transduction / physiology*
-
Trans-Activators / metabolism*
-
Transcription Factors / metabolism
-
Ubiquitin-Protein Ligases
-
Wnt Proteins
-
Wnt-5a Protein
-
beta Catenin
Substances
-
Adenomatous Polyposis Coli Protein
-
CTNNB1 protein, human
-
CTNNB1 protein, mouse
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
NFATC Transcription Factors
-
Nuclear Proteins
-
Proto-Oncogene Proteins
-
Trans-Activators
-
Transcription Factors
-
WNT5A protein, human
-
Wnt Proteins
-
Wnt-5a Protein
-
beta Catenin
-
Ubiquitin-Protein Ligases
-
seven in absentia proteins
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Glycogen Synthase Kinase 3