Delineation of a Fat tumor suppressor pathway
| Autor: | Richard G. Fehon, Eunjoo Cho, Sushmita Maitra, Kenneth D. Irvine, Yongqiang Feng, Cordelia Rauskolb |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Tumor suppressor gene
Cell Cycle Proteins Myosins Protein Serine-Threonine Kinases law.invention law Genetics Melanogaster Animals Drosophila Proteins Genes Tumor Suppressor Transcription factor Neurofibromin 2 biology Kinase Intracellular Signaling Peptides and Proteins Membrane Proteins Nuclear Proteins virus diseases YAP-Signaling Proteins biology.organism_classification Cell biology Merlin (protein) Drosophila melanogaster Gene Expression Regulation Trans-Activators Suppressor Signal transduction Cell Adhesion Molecules Protein Kinases Signal Transduction |
| Zdroj: | Nature Genetics. 38:1142-1150 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng1887 |
| Popis: | Recent studies in Drosophila melanogaster of the protocadherins Dachsous and Fat suggest that they act as ligand and receptor, respectively, for an intercellular signaling pathway that influences tissue polarity, growth and gene expression, but the basis for signaling downstream of Fat has remained unclear. Here, we characterize functional relationships among D. melanogaster tumor suppressors and identify the kinases Discs overgrown and Warts as components of a Fat signaling pathway. fat, discs overgrown and warts regulate a common set of downstream genes in multiple tissues. Genetic experiments position the action of discs overgrown upstream of the Fat pathway component dachs, whereas warts acts downstream of dachs. Warts protein coprecipitates with Dachs, and Warts protein levels are influenced by fat, dachs and discs overgrown in vivo, consistent with its placement as a downstream component of the pathway. The tumor suppressors Merlin, expanded, hippo, salvador and mob as tumor suppressor also share multiple Fat pathway phenotypes but regulate Warts activity independently. Our results functionally link what had been four disparate groups of D. melanogaster tumor suppressors, establish a basic framework for Fat signaling from receptor to transcription factor and implicate Warts as an integrator of multiple growth control signals. |
| Databáze: | OpenAIRE |
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