Document Detail


Reconstitution of dna synthetic capacity in senescent normal human fibroblasts by expressing cellular factors E2F and Mdm2.
MedLine Citation:
PMID:  11640890     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Unraveling the mechanisms underlying cellular senescence will contribute to the understanding of processes involved in aging and cancer. We sought to determine whether expression of cellular factors in senescent WI-38 human fibroblasts was sufficient to induce nuclear DNA synthesis. Expression by recombinant adenovirus of E2F1, E2F2, E2F3, cyclin E/cdk2, and Mdm2 individually resulted in DNA synthesis in 10-30% of cells. However, combination of Mdm2 with E2F or cyclin E/cdk2 resulted in 50 to 75% of cells synthesizing DNA. DNA synthesis occurred approximately 30 h following infection. We conclude that expression of normal cellular factors is sufficient to induce DNA synthesis in senescent normal human fibroblasts.
Authors:
S Sarraj; R Farb; R E Martell
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  270     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-19     Completed Date:  2001-12-07     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  268-76     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Geriatric Research and Education Clinical Center, VA Medical Center, Durham, North Carolina 27705, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
CDC2-CDC28 Kinases*
Cell Aging / physiology*
Cell Cycle / physiology
Cell Cycle Proteins*
Cells, Cultured
Cyclin E / genetics
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / genetics
DNA
DNA-Binding Proteins*
E2F Transcription Factors
E2F1 Transcription Factor
E2F2 Transcription Factor
E2F3 Transcription Factor
Fibroblasts / cytology,  physiology*
Gene Expression / physiology
Humans
Nuclear Proteins*
Protein-Serine-Threonine Kinases / genetics
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-mdm2
Recombinant Proteins / genetics
Signal Transduction / physiology
Transcription Factors / genetics*
Grant Support
ID/Acronym/Agency:
1K08AG/CA00915-01/AG/NIA NIH HHS; 2 P60 AG11268/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin E; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/E2F2 Transcription Factor; 0/E2F2 protein, human; 0/E2F3 Transcription Factor; 0/E2F3 protein, human; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Recombinant Proteins; 0/Transcription Factors; 9007-49-2/DNA; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2

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