A role for ATR in the DNA damage-induced phosphorylation of p53

Randal S. Tibbetts, Kathryn M. Brumbaugh, Josie M. Williams, Jann N. Sarkaria, William A. Cliby, Sheau Yann Shieh, Yoichi Taya, Carol Prives, Robert T. Abraham

Research output: Contribution to journalArticle

800 Scopus citations

Abstract

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 (ATR(ki)) in human fibroblasts inhibited Ser-15 phosphorylation in response to γ-irradiation and UV light. In γ-irradiated cells, ATR(ki) expression selectively interfered with late-phase Ser-15 phosphorylation, whereas ATR(ki) 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.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalGenes and Development
Volume13
Issue number2
DOIs
StatePublished - Jan 15 1999

Keywords

  • ATM
  • ATR
  • P53
  • PIKs
  • Phosphorylation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S. Y., Taya, Y., Prives, C., & Abraham, R. T. (1999). A role for ATR in the DNA damage-induced phosphorylation of p53. Genes and Development, 13(2), 152-157. https://doi.org/10.1101/gad.13.2.152