Document Detail


Lovastatin arrests CHO cells between the origin decision point and the restriction point.
MedLine Citation:
PMID:  11068042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Asynchronously growing Chinese hamster ovary (CHO) cells treated with the pro-drug, beta-lactone ring form of lovastatin were arrested in G(1)-phase. Subsequent removal of lovastatin resulted in the synchronous entry of cells into S-phase regardless of the presence of mevalonic acid. Lovastatin-arrested cells contained hypophosphorylated retinoblastoma protein (Rb) and required serum mitogens to enter S-phase after lovastatin removal, indicating that cell-cycle arrest is prior to the restriction point (R-point). However, in contrast to quiescent cells, intact nuclei prepared from lovastatin-arrested cells were competent for DNA replication when introduced into Xenopus egg extracts. Initiation of replication by Xenopus egg cytosol took place specifically within the dihydrofolate reductase (DHFR) origin locus, demonstrating that cells were arrested after the origin decision point (ODP). We conclude that the beta-lactone ring form of lovastatin is an effective reagent with which to synchronize CHO cells between the ODP and R-point, without resulting in the withdrawal of cells from the cell-cycle into a quiescent state.
Authors:
J R Wu; D M Gilbert
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  FEBS letters     Volume:  484     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-17     Completed Date:  2000-12-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  108-12     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Shanghai Research Center of Life Science, Shanghai Institutes for Biological Sciences, Chineses Academy of Sciences, Shanghai, Japam. wujr@sunm.shcnc.ac.cn
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology
CHO Cells
Cricetinae
DNA Replication / drug effects*
G1 Phase / drug effects*
Lovastatin / pharmacology*
Prodrugs / pharmacology*
Grant Support
ID/Acronym/Agency:
GM57233/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Prodrugs; 75330-75-5/Lovastatin

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


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