Document Detail


The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors.
MedLine Citation:
PMID:  16139224     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sarah K Sjostrom; Greg Finn; William C Hahn; David H Rowitch; Anna Marie Kenney
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental cell     Volume:  9     ISSN:  1534-5807     ISO Abbreviation:  Dev. Cell     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-11-09     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  327-38     Citation Subset:  IM    
Affiliation:
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CDC2 Protein Kinase / physiology*
Cell Cycle / physiology
Cell Line, Tumor
Cerebellum / cytology,  metabolism
Cyclin A / metabolism
Cyclin B / metabolism
Cyclin B1
G1 Phase
Gene Expression Regulation
Glycogen Synthase Kinase 3 / metabolism
Humans
Mice
Mitosis
Neuroblastoma / metabolism*
Neurons / metabolism*,  ultrastructure
Phosphoric Monoester Hydrolases / pharmacology
Phosphorylation
Proto-Oncogene Proteins c-myc / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
K01 CA94223/CA/NCI NIH HHS; NS047527/NS/NINDS NIH HHS; P01 CA50661/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CCNB1 protein, human; 0/Ccnb1 protein, mouse; 0/Cyclin A; 0/Cyclin B; 0/Cyclin B1; 0/MYC protein, human; 0/Myc protein, mouse; 0/Proto-Oncogene Proteins c-myc; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.1.3.-/Phosphoric Monoester Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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