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

Webley, K, Bond, J A, Jones, C J, Blaydes, J P, Craig, A, Hupp, T and Wynford-Thomas, D (2000) Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Molecular and Cellular Biology, 20 (8), 2803-2808.

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.

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Contributors

Author: J P Blaydes

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