PUBLICATION
Zili Inhibits TGF-beta Signaling by Interacting with Smad4
- Authors
- Sun, H., Li, D., Chen, S., Liu, Y., Liao, X., Deng, W., Li, N., Zeng, M., Tao, D., and Ma, Y.
- ID
- ZDB-PUB-091221-8
- Date
- 2010
- Source
- The Journal of biological chemistry 285(6): 4243-4250 (Journal)
- Registered Authors
- Keywords
- CYTOKINES/TGFbeta, DEVELOPMENT DIFFERENTIATION, Gene regulation, SMAD/ transcription factor, Zebra fish, Smad4, TGF-beta, Zili, piwil2
- MeSH Terms
-
- Animals
- Blotting, Western
- Body Patterning/genetics
- Bone Morphogenetic Proteins/genetics
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Epistasis, Genetic
- Female
- Gene Expression Regulation, Developmental
- Immunoprecipitation
- In Situ Hybridization
- Male
- Nodal Protein/genetics
- Oligonucleotides, Antisense/genetics
- Protein Binding
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Receptors, Transforming Growth Factor beta/genetics
- Receptors, Transforming Growth Factor beta/metabolism
- Signal Transduction*
- Smad Proteins, Receptor-Regulated/genetics
- Smad Proteins, Receptor-Regulated/metabolism
- Smad4 Protein/genetics
- Smad4 Protein/metabolism*
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism*
- Two-Hybrid System Techniques
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20007318 Full text @ J. Biol. Chem.
Citation
Sun, H., Li, D., Chen, S., Liu, Y., Liao, X., Deng, W., Li, N., Zeng, M., Tao, D., and Ma, Y. (2010) Zili Inhibits TGF-beta Signaling by Interacting with Smad4. The Journal of biological chemistry. 285(6):4243-4250.
Abstract
Piwi proteins are required for germ cell proliferation, differentiation and germline 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, TGF-beta signaling plays an important role in patterning embryo and control of cell growth and differentiation. Previous study has shown a role for Zili, Piwil2 gene in zebrafish, in germ cell in zebrafish. Here we report that zili functions in patterning 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 BMP signaling. 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 complex to antagonize TGF-beta signaling. This work shows that zili plays a role in early embryogenesis beyond germline as a novel negative regulator of TGF-beta signaling, extending the function of Piwi proteins in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping