β-Arrestin-1 links mitogenic sonic hedgehog signaling to the cell cycle exit machinery in neural precursors
| Autor: | Africa Fernandez-L, Lori A. Mainwaring, Anna Marie Kenney, Cemile G. Guldal, Zaher Nahlé, Susana R. Parathath |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
animal structures
Arrestins Mitosis P300-CBP Transcription Factors Mice Neural Stem Cells Cyclin-dependent kinase Report Cerebellum Animals Hedgehog Proteins p300-CBP Transcription Factors Sonic hedgehog Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Molecular Biology Cells Cultured beta-Arrestins biology Beta-Arrestins Cell Cycle JNK Mitogen-Activated Protein Kinases Cell Biology Cell cycle Hedgehog signaling pathway Cell biology beta-Arrestin 1 embryonic structures biology.protein Signal transduction Smoothened Cyclin-Dependent Kinase Inhibitor p27 Developmental Biology Signal Transduction |
| Zdroj: | Cell cycle (Georgetown, Tex.). 9(19) |
| ISSN: | 1551-4005 |
| Popis: | Development of the cerebellum, a brain region regulating posture and coordination, occurs post-natally and is marked by rapid proliferation of granule neuron precursors (CGNPs), stimulated by mitogenic Sonic hedgehog (Shh) signaling. β-Arrestin (βArr) proteins play important roles downstream of Smoothened, the Shh signal transducer. However, whether Shh regulates βArrs and what role they play in Shh-driven CGNP proliferation remains to be determined. Here, we report that Shh induces βArr1 accumulation and localization to the nucleus, where it participates in enhancing expression of the cyclin dependent kinase (cdk) inhibitor p27, whose accumulation eventually drives CGNP cell cycle exit. βArr1 knockdown enhances CGNP proliferation and reduces p27 expression. Thus, Shh-mediated βArr1 induction represents a novel negative feedback loop within the Shh mitogenic pathway, such that ongoing Shh signaling, while required for CGNPs to proliferate, also sets up a cell-intrinsic clock programming their ultimate exit from the cell cycle. |
| Databáze: | OpenAIRE |
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