Abstract
Axin, APC, and the kinase GSK3 beta are part of a destruction complex that regulates the stability of the Wnt pathway effector beta-catenin. In C. elegans, several Wnt-controlled developmental processes have been described, but an Axin ortholog has not been found in the genome sequence and SGG-1/GSK3 beta, and the APC-related protein APR-1 have been shown to act in a positive, rather than negative fashion in Wnt signaling. We have shown previously that the EGL-20/Wnt-dependent expression of the homeobox gene mab-5 in the Q neuroblast lineage requires BAR-1/beta-catenin and POP-1/Tcf. Here, we have investigated how BAR-1 is regulated by the EGL-20 pathway. First, we have characterized a negative regulator of the EGL-20 pathway, pry-1. We show that pry-1 encodes an RGS and DIX domain-containing protein that is distantly related to Axin/Conductin. Our results demonstrate that despite its sequence divergence, PRY-1 is a functional Axin homolog. We show that PRY-1 interacts with BAR-1, SGG-1, and APR-1 and that overexpression of PRY-1 inhibits mab-5 expression. Furthermore, pry-1 rescues the zebrafish axin1 mutation masterblind, showing that it can functionally interact with vertebrate destruction complex components. Finally, we show that SGG-1, in addition to its positive regulatory role in early embryonic Wnt signaling, may function as a negative regulator of the EGL-20 pathway. We conclude that a highly divergent destruction complex consisting of PRY-1, SGG-1, and APR-1 regulates BAR-1/beta-catenin signaling in C. elegans.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenomatous Polyposis Coli Protein / metabolism
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Amino Acid Sequence
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Animals
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Axin Protein
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental
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Glycogen Synthase Kinase 3
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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Green Fluorescent Proteins
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Helminth Proteins / physiology*
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High Mobility Group Proteins / metabolism
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Hot Temperature
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Insect Proteins / metabolism
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Intercellular Signaling Peptides and Proteins
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Luminescent Proteins / metabolism
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Molecular Sequence Data
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Mutation
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Phenotype
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Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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Suppression, Genetic
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Tissue Inhibitor of Metalloproteinase-3
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Tissue Inhibitor of Metalloproteinases / metabolism
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Trans-Activators*
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Wnt Proteins
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Zebrafish Proteins*
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beta Catenin
Substances
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AXIN1 protein, human
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Adenomatous Polyposis Coli Protein
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Axin Protein
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Egl-20 protein, C elegans
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Glycoproteins
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Helminth Proteins
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High Mobility Group Proteins
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Insect Proteins
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Intercellular Signaling Peptides and Proteins
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Luminescent Proteins
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Proteins
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Proto-Oncogene Proteins
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Pry-1 protein, C elegans
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Repressor Proteins
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TIMP3 protein, human
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Tissue Inhibitor of Metalloproteinase-3
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Tissue Inhibitor of Metalloproteinases
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Trans-Activators
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Wnt Proteins
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Zebrafish Proteins
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bar-1 protein, C elegans
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beta Catenin
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pop-1 protein, C elegans
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wnt8b protein, zebrafish
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APR-1 pheromone-binding protein, Antheraea pernyi
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Green Fluorescent Proteins
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3