Abstract
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 language | English |
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Pages (from-to) | 2803-8 |
Number of pages | 6 |
Journal | Molecular and Cellular Biology |
Volume | 20 |
Issue number | 8 |
Publication status | Published - 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