Reconstitution of dna synthetic capacity in senescent normal human fibroblasts by expressing cellular factors E2F and Mdm2

Exp Cell Res. 2001 Nov 1;270(2):268-76. doi: 10.1006/excr.2001.5352.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • CDC2-CDC28 Kinases*
  • Cell Cycle / physiology
  • Cell Cycle Proteins*
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • 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
  • Fibroblasts / 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*

Substances

  • Cell Cycle Proteins
  • Cyclin E
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2F2 Transcription Factor
  • E2F2 protein, human
  • E2F3 Transcription Factor
  • E2F3 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Transcription Factors
  • DNA
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases