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

doi:10.1101/gad.13.2.152

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 journal › Article › peer-review

826 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 language	English (US)
Pages (from-to)	152-157
Number of pages	6
Journal	Genes and Development
Volume	13
Issue number	2
DOIs	https://doi.org/10.1101/gad.13.2.152
State	Published - Jan 15 1999

Keywords

ATM
ATR
P53
PIKs
Phosphorylation

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.13.2.152

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title = "A role for ATR in the DNA damage-induced phosphorylation of p53",

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.",

keywords = "ATM, ATR, P53, PIKs, Phosphorylation",

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AU - Tibbetts, Randal S.

AU - Brumbaugh, Kathryn M.

AU - Williams, Josie M.

AU - Sarkaria, Jann N.

AU - Cliby, William A.

AU - Shieh, Sheau Yann

AU - Taya, Yoichi

AU - Prives, Carol

AU - Abraham, Robert T.

PY - 1999/1/15

Y1 - 1999/1/15

N2 - 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.

AB - 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.

KW - ATM

KW - ATR

KW - P53

KW - PIKs

KW - Phosphorylation

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

Abstract

Keywords

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