Document Detail

CDC-25.1 stability is regulated by distinct domains to restrict cell division during embryogenesis in C. elegans.
MedLine Citation:
PMID:  18287204     Owner:  NLM     Status:  MEDLINE    
Cdc25 phosphatases are key positive cell cycle regulators that coordinate cell divisions with growth and morphogenesis in many organisms. Intriguingly in C. elegans, two cdc-25.1(gf) mutations induce tissue-specific and temporally restricted hyperplasia in the embryonic intestinal lineage, despite stabilization of the mutant CDC-25.1 protein in every blastomere. We investigated the molecular basis underlying the CDC-25.1(gf) stabilization and its associated tissue-specific phenotype. We found that both mutations affect a canonical beta-TrCP phosphodegron motif, while the F-box protein LIN-23, the beta-TrCP orthologue, is required for the timely degradation of CDC-25.1. Accordingly, depletion of lin-23 in wild-type embryos stabilizes CDC-25.1 and triggers intestinal hyperplasia, which is, at least in part, cdc-25.1 dependent. lin-23(RNAi) causes embryonic lethality owing to cell fate transformations that convert blastomeres to an intestinal fate, sensitizing them to increased levels of CDC-25.1. Our characterization of a novel destabilizing cdc-25.1(lf) intragenic suppressor that acts independently of lin-23 indicates that additional cues impinge on different motifs of the CDC-25.1 phosphatase during early embryogenesis to control its stability and turnover, in order to ensure the timely divisions of intestinal cells and coordinate them with the formation of the developing gut.
Michaël Hebeisen; Richard Roy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-02-20
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  135     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-10     Completed Date:  2008-06-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1259-69     Citation Subset:  IM    
Department of Biology, McGill University, Montreal, Quebec, H3A 1B1, Canada.
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MeSH Terms
Amino Acid Motifs
Amino Acid Sequence
Animals, Genetically Modified
Caenorhabditis elegans / cytology,  embryology*,  genetics*
Caenorhabditis elegans Proteins / genetics
Cell Cycle
Cell Cycle Proteins / genetics
Cell Division*
Cell Lineage
Embryo, Nonmammalian
Embryonic Development*
F-Box Proteins / genetics
Gene Expression Regulation, Developmental
Green Fluorescent Proteins / metabolism
Intestines / cytology,  metabolism
Molecular Sequence Data
Protein Structure, Tertiary
RNA Interference
RNA, Helminth / genetics
cdc25 Phosphatases / genetics*
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Cell Cycle Proteins; 0/F-Box Proteins; 0/RNA, Helminth; 0/lin-23 protein, C elegans; 147336-22-9/Green Fluorescent Proteins; EC Phosphatases

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