期刊
DEVELOPMENTAL CELL
卷 9, 期 3, 页码 327-338出版社
CELL PRESS
DOI: 10.1016/j.devcel.2005.07.014
关键词
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资金
- NCI NIH HHS [P01 CA50661, K01 CA94223] Funding Source: Medline
- NINDS NIH HHS [NS047527] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA050661, K01CA094223] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS047527] Funding Source: NIH RePORTER
Myc family transcription factors are destabilized by phosphorylation of a conserved amino-terminal GSK-3 beta motif. In proliferating cerebellar granule neuron precursors (CGNPs), Sonic hedgehog signaling induces N-myc expression, and N-myc protein is stabilized by insulin-like growth factor-mediated suppression of GSK-3 beta. N-myc phosphorylation-mediated degradation is a prerequisite for CGNP growth arrest and differentiation. We investigated whether N-myc phosphorylation and turnover are thus linked to cell cycle exit in primary mouse CGNP cultures and the developing cerebellum. We report that phosphorylation-induced turnover of endogenous N-myc protein in CGNPs increases during mitosis, due to increased priming phosphorylation of N-myc for GSK-3 beta. The priming phosphorylation requires the Cdk1 complex, whose cyclin subunits are indirect Sonic hedgehog targets. These findings provide a mechanism for promoting growth arrest in the final cycle of neural precursor proliferation competency, or for resetting the cell cycle in the G1 phase, by destabilizing N-myc in mitosis.
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