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

  • Tibbetts R
  • Brumbaugh K
  • Williams J
 et al. 
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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 (ATRki) in human fibroblasts inhibited Ser-15 phosphorylation in response to gamma-irradiation and UV light. In gamma-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.

Author-supplied keywords

  • ATM
  • ATR
  • P53
  • PIKs
  • Phosphorylation

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Authors

  • Randal S. Tibbetts

  • Kathryn M. Brumbaugh

  • Josie M. Williams

  • Jann N. Sarkaria

  • William A. Cliby

  • Sheau Yann Shieh

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