Document Detail

Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing.
MedLine Citation:
PMID:  15084262     Owner:  NLM     Status:  MEDLINE    
Many types of cells compensate for induced alterations in the length of one cell cycle phase (G1, S, or G2) by altering the lengths of the other phases. Here we show that, when cells in Drosophila wing discs are delayed in G1, they maintain normal division rates by accelerating passage through S and G2. Similarly, when G2-->M progression is retarded, G1-->S progression accelerates. This compensation mechanism employs negative feedback in which the cyclin-dependent kinases Cdk1 and Cdk2 downregulate the transcription factor dE2F1. dE2F1, in turn, positively regulates cyclin E and string/cdc25, which activate the Cdks to drive cell cycle progression. This homeostatic mechanism coordinates rates of G1-->S and G2-->M progression, maintaining normal rates of proliferation when cell cycle controls are perturbed (e.g., by ectopic Dacapo, dWee1, dMyc, or Rheb). Without dE2F1, the compensatory mechanism fails, and treatments that alter Cdk activity cause aberrant cell cycle timing and cell death.
Tânia Reis; Bruce A Edgar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell     Volume:  117     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-15     Completed Date:  2004-05-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-64     Citation Subset:  IM    
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
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MeSH Terms
Cell Cycle / genetics*
Cell Cycle Proteins / genetics,  metabolism*
Cyclin E / genetics,  metabolism
Cyclin-Dependent Kinases / genetics,  metabolism*
DNA-Binding Proteins*
Down-Regulation / genetics
Drosophila Proteins / genetics
Drosophila melanogaster / genetics,  metabolism*
E2F Transcription Factors
Feedback, Physiological / genetics,  physiology*
G1 Phase / genetics
G2 Phase / genetics
Gene Expression Regulation, Developmental / genetics
Protein Tyrosine Phosphatases / genetics
Transcription Factors / genetics,  metabolism*
Wing / cytology,  growth & development,  metabolism
Grant Support
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin E; 0/DNA-Binding Proteins; 0/Drosophila Proteins; 0/E2F Transcription Factors; 0/Transcription Factors; EC Kinases; EC Tyrosine Phosphatases; EC protein, Drosophila

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