Document Detail

Cyclin D1 production in cycling cells depends on ras in a cell-cycle-specific manner.
MedLine Citation:
PMID:  10531005     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cellular Ras and cyclin D1 are required at similar times of the cell cycle in quiescent NIH3T3 cells that have been induced to proliferate, but not in the case of cycling NIH3T3 cells. In asynchronous cultures, Ras activity has been found to be required only during G2 phase to promote passage through the entire upcoming cell cycle, whereas cyclin D1 is required through G1 phase until DNA synthesis begins. To explain these results in molecular terms, we propose a model whereby continuous cell cycle progression in NIH3T3 cells requires cellular Ras activity to promote the synthesis of cyclin D1 during G2 phase. Cyclin D1 expression then continues through G1 phase independently of Ras activity, and drives the G1-S phase transition. RESULTS: We found high levels of cyclin D1 expression during the G2, M and G1 phases of the cell cycle in cycling NIH3T3 cells, using quantitative fluorescent antibody measurements of individual cells. By microinjecting anti-Ras antibody, we found that the induction of cyclin D1 expression beginning in G2 phase was dependent on Ras activity. Consistent with our model, cyclin D1 expression during G1 phase was particularly stable following neutralization of cellular Ras. Finally, ectopic expression of cyclin D1 largely overcame the requirement for cellular Ras activity during the continuous proliferation of cycling NIH3T3 cells. CONCLUSIONS: Ras-dependent induction of cyclin D1 expression beginning in G2 phase is critical for continuous cell cycle progression in NIH3T3 cells.
M Hitomi; D W Stacey
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Current biology : CB     Volume:  9     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  2000-03-09     Completed Date:  2000-03-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1075-84     Citation Subset:  IM    
Department of Molecular Biology The Lerner Research Institute The Cleveland Clinic Foundation 9500 Euclid Avenue, Cleveland, Ohio, 44195, USA.
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MeSH Terms
3T3 Cells
Blotting, Western
Cell Cycle*
Cyclin D1 / biosynthesis*,  metabolism
DNA / metabolism
G2 Phase / physiology
Microscopy, Fluorescence
Microscopy, Video
S Phase / physiology
Time Factors
ras Proteins / physiology*
Grant Support
Reg. No./Substance:
136601-57-5/Cyclin D1; 9007-49-2/DNA; EC Proteins

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

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