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 Arthur Cliby, Sheau Yann Shieh, Yoichi Taya, Carol Prives, Robert T. Abraham

Research output: Contribution to journalArticle

789 Citations (Scopus)

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
StatePublished - Jan 15 1999

Fingerprint

DNA Damage
Phosphorylation
DNA
Ultraviolet Rays
Up-Regulation
Fibroblasts
Proteins

Keywords

  • ATM
  • ATR
  • P53
  • Phosphorylation
  • PIKs

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S. Y., ... Abraham, R. T. (1999). A role for ATR in the DNA damage-induced phosphorylation of p53. Genes and Development, 13(2), 152-157.

A role for ATR in the DNA damage-induced phosphorylation of p53. / Tibbetts, Randal S.; Brumbaugh, Kathryn M.; Williams, Josie M.; Sarkaria, Jann N; Cliby, William Arthur; Shieh, Sheau Yann; Taya, Yoichi; Prives, Carol; Abraham, Robert T.

In: Genes and Development, Vol. 13, No. 2, 15.01.1999, p. 152-157.

Research output: Contribution to journalArticle

Tibbetts, RS, Brumbaugh, KM, Williams, JM, Sarkaria, JN, Cliby, WA, Shieh, SY, Taya, Y, Prives, C & Abraham, RT 1999, 'A role for ATR in the DNA damage-induced phosphorylation of p53', Genes and Development, vol. 13, no. 2, pp. 152-157.
Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes and Development. 1999 Jan 15;13(2):152-157.
Tibbetts, Randal S. ; Brumbaugh, Kathryn M. ; Williams, Josie M. ; Sarkaria, Jann N ; Cliby, William Arthur ; Shieh, Sheau Yann ; Taya, Yoichi ; Prives, Carol ; Abraham, Robert T. / A role for ATR in the DNA damage-induced phosphorylation of p53. In: Genes and Development. 1999 ; Vol. 13, No. 2. pp. 152-157.
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