Identification of novel candidates for replicative senescence by functional proteomics

Silvia Benvenuti, Rainer Cramer, Jim Bruce, Michael D. Waterfield, Parmjit S. Jat

Research output: Contribution to journalArticlepeer-review

Abstract

To identify the underlying mechanisms that limit the mitotic potential of normal somatic cells, we have undertaken a high resolution differential proteomic analysis aimed at identifying proteins that were differentially expressed upon replicative senescence. Since replicative senescence in heterogenous primary fibroblast cultures is asynchronous, we analysed a group of conditionally immortalized rat embryo fibroblast cell lines that have previously been shown to undergo synchronous senescence upon inactivation of SV40 tsA58 T antigen. This identified 43 spots that were differentially expressed in these cell lines. Comparison of the identity of these features with those identified in a complimentary independent differential proteomic analysis of replicative senescence, directly in primary rat embryo fibroblasts upon serial passaging, identified nine features that were in common between the two studies even though they had been conducted entirely separately. None of these proteins have previously been recognized to be involved with replicative senescence. Thus, they represent novel starting points for elucidating the underlying mechanism that regulates the finite mitotic life span of somatic cells and how it can be overcome in cancer cells.

Original languageEnglish
Pages (from-to)4403-4413
Number of pages11
JournalOncogene
Volume21
Issue number28
DOIs
Publication statusPublished - Jun 27 2002

Keywords

  • Gene expression
  • Mass spectrometry
  • Proteomics
  • Replicative senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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