A role for ATR in the DNA damage-induced phosphorylation of p53
AUTOR(ES)
Tibbetts, Randal S.
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Phosphorylation at Ser-15 may be a critical event in the up-regulation and functional activation of p53 during cellular stress. In this report we provide evidence that the ATM–Rad3-related protein ATR regulates phosphorylation of Ser-15 in DNA-damaged cells. Overexpression of catalytically inactive ATR (ATRki) in human fibroblasts inhibited Ser-15 phosphorylation in response to γ-irradiation and UV light. In γ-irradiated cells, ATRki expression selectively interfered with late-phase Ser-15 phosphorylation, whereas ATRki blocked UV-induced Ser-15 phosphorylation in a time-independent manner. ATR phosphorylated p53 at Ser-15 and Ser-37 in vitro, suggesting that p53 is a target for phosphorylation by ATR in DNA-damaged cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=316393Documentos Relacionados
- Phospholipase D Elevates the Level of MDM2 and Suppresses DNA Damage-Induced Increases in p53
- Supramolecular Complex Formation between Rad6 and Proteins of the p53 Pathway during DNA Damage-Induced Response
- DNA damage-induced apoptosis requires the DNA-dependent protein kinase, and is mediated by the latent population of p53
- DNA damage-induced apoptosis requires the DNA-dependent protein kinase, and is mediated by the latent population of p53
- Modulation of DNA damage-induced apoptosis by cell adhesion is independently mediated by p53 and c-Abl