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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
1999-8-17
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pubmed:abstractText |
Levels of the tumour suppressor protein p53 are increased in response to a variety of DNA damaging agents. DNA damage-induced phosphorylation of p53 occurs at serine-15 in vivo. Phosphorylation of p53 at serine-15 leads to a stabilization of the polypeptide by inhibiting its interaction with Mdm2, a protein that targets p53 for ubiquitin-dependent degradation. However, the mechanisms by which DNA damage is signalled to p53 remain unclear. Here, we report the identification of a novel DNA-activated protein kinase that phosphorylates p53 on serine-15. Fractionation of HeLa nuclear extracts and biochemical analyses indicate that this kinase is distinct from the DNA-dependent protein kinase (DNA-PK) and corresponds to the human cell cycle checkpoint protein ATR. Immunoprecipitation studies of recombinant ATR reveal that catalytic activity of this polypeptide is required for DNA-stimulated phosphorylation of p53 on serine-15. These data suggest that ATR may function upstream of p53 in a signal transduction cascade initiated upon DNA damage and provide a biochemical assay system for ATR activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...,
http://linkedlifedata.com/resource/pubmed/chemical/p21-Activated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3989-95
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:10435622-Ataxia Telangiectasia,
pubmed-meshheading:10435622-Catalysis,
pubmed-meshheading:10435622-Cell Cycle Proteins,
pubmed-meshheading:10435622-DNA,
pubmed-meshheading:10435622-DNA-Activated Protein Kinase,
pubmed-meshheading:10435622-DNA-Binding Proteins,
pubmed-meshheading:10435622-HeLa Cells,
pubmed-meshheading:10435622-Humans,
pubmed-meshheading:10435622-Nuclear Proteins,
pubmed-meshheading:10435622-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10435622-Phosphorylation,
pubmed-meshheading:10435622-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10435622-Proteins,
pubmed-meshheading:10435622-Serine,
pubmed-meshheading:10435622-Tumor Suppressor Protein p53,
pubmed-meshheading:10435622-Tumor Suppressor Proteins,
pubmed-meshheading:10435622-p21-Activated Kinases
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pubmed:year |
1999
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pubmed:articleTitle |
The ataxia-telangiectasia related protein ATR mediates DNA-dependent phosphorylation of p53.
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pubmed:affiliation |
Wellcome Trust/Cancer Research Campaign Institute of Cancer and Developmental Biology, Department of Zoology, Cambridge University, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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