The Arf Tumor Suppressor Regulates Platelet-Derived Growth Factor Receptor ? Signaling: A New View through the Eyes of Arf-/- Mice
| Autor: | Stephen X. Skapek, J. Derek Thornton, Ricardo L.A. Silva, Amy C. Martin |
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| Rok vydání: | 2005 |
| Předmět: |
Genotype
Tumor suppressor gene Regulator Eye Mural cell law.invention Receptor Platelet-Derived Growth Factor beta Gene product Mice Growth factor receptor law Tumor Suppressor Protein p14ARF Animals Humans Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Mice Knockout biology Cell Biology Cell biology biology.protein Mdm2 Suppressor Platelet-derived growth factor receptor Signal Transduction Developmental Biology |
| Zdroj: | Cell Cycle. 4:1316-1319 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.4.10.2109 |
| Popis: | Arf is a key mammalian tumor suppressor gene known to be activated in response to aberrant mitogenic signals leading to both p53-dependent and -independent effects. We recently uncovered a new and somewhat unexpected function for mouse Arf as a regulator of mural cell accumulation within an ocular vascular bed destined to regress in the postnatal period. We found that the Arf gene product, p19(Arf), blocks mural cell proliferation driven by Platelet-derived growth factor receptor beta (Pdgfrbeta) in the developing vitreous. In vivo studies and analyses of cultured cells indicate that p19(Arf) dampens the expression of Pdgfrbeta. In cultured mouse embryo fibroblasts, p19(Arf) accomplishes this independently of two established effectors - Mdm2 and p53. Our findings indicating that p19(Arf) responds to specific developmental cues to disrupt Pdgfrbeta signaling in the developing eye extend existing paradigms for Arf tumor suppressor gene biology. |
| Databáze: | OpenAIRE |
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