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Zili Inhibits Transforming Growth Factor-β Signaling by Interacting with Smad4
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Piwi proteins are required for germ cell proliferation, differentiation, and germ line stem cell maintenance. In normal tissues, human and mouse Piwil2 are primarily expressed in testis but widely expressed in tumors. However, the underlying mechanism remains largely unknown. In vertebrates, transforming growth factor (TGF)-beta signaling plays an important role in patterning embryo and control of cell growth and differentiation. A previous study has shown a role for Zili, a Piwil2 gene in zebrafish, in germ cells in zebrafish. Here we report that zili functions in patterning the early embryo and inhibits TGF-beta signaling. Whole mount expression analysis shows that zili expresses not only in PGCs but also in axis. Ectopic expression of zili causes fusion of the eyes and reduction of mesodermal marker genes expression, suggesting that zili functions to inhibit Nodal signaling and mesoderm formation. Genetic interaction shows that zili inhibits Nodal and bone morphogenetic protein signaling. The results of protein interaction assays identify that Zili binds to Smad4 via its N-terminal domain and prevents the formation of Smad2/3/4 and Smad1/5/9/4 complexes to antagonize TGF-beta signaling. This work shows that zili plays a role in early embryogenesis beyond germ line as a novel negative regulator of TGF-beta signaling, extending the function of Piwi proteins in vertebrates.
- Subjects :
- TGF-β
Male
Cytokines/TGF-β
Embryo, Nonmammalian
Nodal Protein
Blotting, Western
Nodal signaling
Piwi-interacting RNA
Biochemistry
Development Differentiation
Germ cell proliferation
Transforming Growth Factor beta
Two-Hybrid System Techniques
Animals
Immunoprecipitation
Gene Regulation
Molecular Biology
Zebrafish
Smad/Transcription Factor
In Situ Hybridization
Body Patterning
Smad4 Protein
Piwil2
biology
Zebra fish
Mechanisms of Signal Transduction
Gene Expression Regulation, Developmental
RNA-Binding Proteins
Zili
Epistasis, Genetic
Cell Biology
Transforming growth factor beta
Oligonucleotides, Antisense
Zebrafish Proteins
biology.organism_classification
Smad Proteins, Receptor-Regulated
Molecular biology
Cell biology
Bone Morphogenetic Proteins
Mesoderm formation
biology.protein
Female
Ectopic expression
Smad4
NODAL
Receptors, Transforming Growth Factor beta
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....fbdd00e935cd4e436f69f32d30975b9a