The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans
| العنوان: | The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans |
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| المؤلفون: | Hans Clevers, Hendrik C. Korswagen, Sandra van de Water, Damien Coudreuse, Danica Zivkovic, Marco C. Betist |
| المصدر: | Genes & Development. 16:1291-1302 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Hot Temperature, Glycogen Synthase Kinase 3, Suppression, Genetic, GSK-3, Zebrafish, beta Catenin, Caenorhabditis elegans, Genetics, biology, High Mobility Group Proteins, Wnt signaling pathway, Gene Expression Regulation, Developmental, Tissue Inhibitor of Metalloproteinases, LRP5, Helminth Proteins, Cell biology, DNA-Binding Proteins, Phenotype, Insect Proteins, Intercellular Signaling Peptides and Proteins, Research Paper, Signal Transduction, animal structures, Beta-catenin, Adenomatous Polyposis Coli Protein, Green Fluorescent Proteins, Molecular Sequence Data, Axin Protein, Proto-Oncogene Proteins, AXIN1, Animals, Amino Acid Sequence, Caenorhabditis elegans Proteins, Glycoproteins, Tissue Inhibitor of Metalloproteinase-3, Sequence Homology, Amino Acid, Proteins, Zebrafish Proteins, biology.organism_classification, Repressor Proteins, Wnt Proteins, Cytoskeletal Proteins, Luminescent Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Mutation, Trans-Activators, biology.protein, Carrier Proteins, Developmental Biology |
| الوصف: | Axin, APC, and the kinase GSK3β are part of a destruction complex that regulates the stability of the Wnt pathway effector β-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/GSK3β, 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/β-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 inhibitsmab-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/β-catenin signaling in C. elegans. |
| تدمد: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.981802 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bcbe66f17809a95263266b341aea548 https://doi.org/10.1101/gad.981802 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8bcbe66f17809a95263266b341aea548 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495477 08909369 |
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| DOI: | 10.1101/gad.981802 |