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PMID: 9925639 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 13 ·No. 2 ·1999-01-15 ·Pages 152-7

Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, Taya Y, Prives C, Abraham RT

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.

MeSH Terms
Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins/genetics,metabolism DNA Damage/physiology,radiation effects DNA-Binding Proteins Doxycycline/pharmacology Fibroblasts Gamma Rays Humans K562 Cells Mutation Phosphorylation/drug effects,radiation effects Precipitin Tests Protein Serine-Threonine Kinases Proteins/metabolism Recombinant Fusion Proteins/biosynthesis,immunology,metabolism Serine/metabolism Time Factors Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism Tumor Suppressor Proteins Ultraviolet Rays
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Proteins Recombinant Fusion Proteins Tumor Suppressor Protein p53 Tumor Suppressor Proteins Serine ATM protein, human ATR protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Doxycycline
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Tibbetts R S
Department of Pharmacology and Cancer Cell Biology, Duke University, Durham, North Carolina 27710 USA.
Brumbaugh K M
Williams J M
Sarkaria J N
Cliby W A
Shieh S Y
Taya Y
Prives C
Abraham R T
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35 references, click to expand
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.2.152
Published
1999-01-15
Pages
152-7
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316393
Subset
IM
Grants
NCI NIH HHS · CA58316 · United States
NCI NIH HHS · CA52995 · United States
NCI NIH HHS · CA76193 · United States
External Links
PubMed source DOI: 10.1101/gad.13.2.152 PMC Full Text View journal details
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