Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage

K Webley, J A Bond, C J Jones, J P Blaydes, A Craig, T Hupp, D Wynford-Thomas

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Replicative senescence in human fibroblasts is absolutely dependent on the function of the phosphoprotein p53 and correlates with activation of p53-dependent transcription. However, no evidence for posttranslational modification of p53 in senescence has been presented, raising the possibility that changes in transcriptional activity result from upregulation of a coactivator. Using a series of antibodies with phosphorylation-sensitive epitopes, we now show that senescence is associated with major changes at putative regulatory sites in the N and C termini of p53 consistent with increased phosphorylation at serine-15, threonine-18, and serine-376 and decreased phosphorylation at serine-392. Ionizing and UV radiation generated overlapping but distinct profiles of response, with increased serine-15 phosphorylation being the only common change. These results support a direct role for p53 in signaling replicative senescence and are consistent with the generation by telomere erosion of a signal which shares some but not all of the features of DNA double-strand breaks.
Original languageEnglish
Pages (from-to)2803-8
Number of pages6
JournalMolecular and Cellular Biology
Volume20
Issue number8
Publication statusPublished - Apr 2000

Keywords / Materials (for Non-textual outputs)

  • Cell Line
  • DNA Damage
  • DNA Replication
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Protein Processing, Post-Translational
  • Tumor Suppressor Protein p53
  • Ultraviolet Rays

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