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rdf:type |
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lifeskim:mentions |
umls-concept:C0031715,
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0243127,
umls-concept:C0439855,
umls-concept:C0443331,
umls-concept:C0599851,
umls-concept:C0600138,
umls-concept:C0812287,
umls-concept:C1332721,
umls-concept:C1709634,
umls-concept:C1998811
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pubmed:issue |
3
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pubmed:dateCreated |
2005-9-5
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pubmed:abstractText |
Myc family transcription factors are destabilized by phosphorylation of a conserved amino-terminal GSK-3beta 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-3beta. 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-3beta. 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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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2 Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/MYC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Myc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1534-5807
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
327-38
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:16139224-Animals,
pubmed-meshheading:16139224-CDC2 Protein Kinase,
pubmed-meshheading:16139224-Cell Cycle,
pubmed-meshheading:16139224-Cell Line, Tumor,
pubmed-meshheading:16139224-Cerebellum,
pubmed-meshheading:16139224-Cyclin A,
pubmed-meshheading:16139224-Cyclin B,
pubmed-meshheading:16139224-Cyclin B1,
pubmed-meshheading:16139224-G1 Phase,
pubmed-meshheading:16139224-Gene Expression Regulation,
pubmed-meshheading:16139224-Glycogen Synthase Kinase 3,
pubmed-meshheading:16139224-Humans,
pubmed-meshheading:16139224-Mice,
pubmed-meshheading:16139224-Mitosis,
pubmed-meshheading:16139224-Neuroblastoma,
pubmed-meshheading:16139224-Neurons,
pubmed-meshheading:16139224-Phosphoric Monoester Hydrolases,
pubmed-meshheading:16139224-Phosphorylation,
pubmed-meshheading:16139224-Proto-Oncogene Proteins c-myc
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pubmed:year |
2005
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pubmed:articleTitle |
The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors.
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pubmed:affiliation |
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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