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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2003-10-13
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pubmed:abstractText |
Phosphorylation of mouse p53 at Ser18 occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser18 to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage. p53 protein stabilization and DNA binding are similar in knock-in and wild type mice, but C-terminal acetylation was defective, consistent with a role for Ser18 in the recruitment of transcriptional co-activators. The apoptotic response of knock-in thymocytes to ionizing radiation is intermediate between that of wild type and p53 null thymocytes. Despite impaired transcriptional and apoptotic responses, the knock-in mice are not prone to spontaneous tumorigenesis. This indicates that neither phosphorylation of p53 on Ser18 by ATM nor a full transcriptional response is essential to prevent spontaneous tumor formation in mice.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41028-33
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:12909629-Animals,
pubmed-meshheading:12909629-Apoptosis,
pubmed-meshheading:12909629-Blotting, Western,
pubmed-meshheading:12909629-Cell Cycle,
pubmed-meshheading:12909629-Cell Cycle Proteins,
pubmed-meshheading:12909629-Chromatin,
pubmed-meshheading:12909629-DNA Damage,
pubmed-meshheading:12909629-DNA-Binding Proteins,
pubmed-meshheading:12909629-Dose-Response Relationship, Radiation,
pubmed-meshheading:12909629-Fibroblasts,
pubmed-meshheading:12909629-Mice,
pubmed-meshheading:12909629-Mice, Transgenic,
pubmed-meshheading:12909629-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:12909629-Phosphorylation,
pubmed-meshheading:12909629-Precipitin Tests,
pubmed-meshheading:12909629-Promoter Regions, Genetic,
pubmed-meshheading:12909629-Protein Structure, Tertiary,
pubmed-meshheading:12909629-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12909629-RNA, Messenger,
pubmed-meshheading:12909629-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12909629-Serine,
pubmed-meshheading:12909629-Thymus Gland,
pubmed-meshheading:12909629-Time Factors,
pubmed-meshheading:12909629-Transcription, Genetic,
pubmed-meshheading:12909629-Transcriptional Activation,
pubmed-meshheading:12909629-Tumor Suppressor Protein p53,
pubmed-meshheading:12909629-Tumor Suppressor Proteins,
pubmed-meshheading:12909629-Ultraviolet Rays
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pubmed:year |
2003
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pubmed:articleTitle |
Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses.
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pubmed:affiliation |
Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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