PUBLICATION
The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans
- Authors
- Korswagen, H.C., Coudreuse, D.Y., Betist, M.C., van de Water, S., Zivkovic, D., and Clevers, H.C.
- ID
- ZDB-PUB-020701-4
- Date
- 2002
- Source
- Genes & Development 16(10): 1291-1302 (Journal)
- Registered Authors
- Jongejan-Zivkovic, Dana
- Keywords
- none
- MeSH Terms
-
- Adenomatous Polyposis Coli Protein/metabolism
- Amino Acid Sequence
- Animals
- Axin Protein
- Caenorhabditis elegans/genetics*
- Caenorhabditis elegans/growth & development
- Caenorhabditis elegans/metabolism*
- Caenorhabditis elegans Proteins*
- Calcium-Calmodulin-Dependent Protein Kinases/metabolism
- Carrier Proteins/metabolism
- Cytoskeletal Proteins/metabolism
- DNA-Binding Proteins/metabolism
- Gene Expression Regulation, Developmental
- Glycogen Synthase Kinase 3
- Glycoproteins/genetics
- Glycoproteins/metabolism*
- Green Fluorescent Proteins
- Helminth Proteins/physiology*
- High Mobility Group Proteins/metabolism
- Hot Temperature
- Insect Proteins/metabolism
- Luminescent Proteins/metabolism
- Molecular Sequence Data
- Mutation
- Phenotype
- Proteins/metabolism
- Proto-Oncogene Proteins/physiology*
- Repressor Proteins*
- Sequence Homology, Amino Acid
- Signal Transduction/physiology*
- Suppression, Genetic
- Tissue Inhibitor of Metalloproteinase-3
- Tissue Inhibitor of Metalloproteinases/metabolism
- Trans-Activators*
- Wnt Proteins
- Zebrafish Proteins*
- beta Catenin
- PubMed
- 12023307 Full text @ Genes & Dev.
Citation
Korswagen, H.C., Coudreuse, D.Y., Betist, M.C., van de Water, S., Zivkovic, D., and Clevers, H.C. (2002) The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans. Genes & Development. 16(10):1291-1302.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping