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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-2-15
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pubmed:abstractText |
Recognition of certain types of DNA lesions by the tumor suppressor protein, p53, represents one of the several downstream functions of this protein in response to DNA damage. This binding property is regulated by several factors including posttranslational modifications and interactions with other proteins. Phosphorylation by several stress-response kinases activates p53 by increasing protein stability as well as transactivation properties. Here we examined the effect of phosphorylation events on the sequence-independent binding properties of p53 using two DNA substrates: One resembling Holliday junctions and the other containing extra base bulges. Gel retardation assays showed that dephosphorylation of serine 392 in the C-terminal domain of p53 greatly reduces Holliday junction and lesion recognition. In contrast, sequence-specific binding is disrupted by the removal of some N-terminal phosphates but not serine 392. Rephosphorylation of p53 by certain kinases can restore p53 recognition of Holliday junctions and 3-cytosine bulges. In all cases, phosphorylation of serine 392 occurs; however, reactivation also involves other residues. Together, the results show that p53 DNA binding activity is strongly regulated by the phosphorylation state of the protein.
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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/Casein Kinase I,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Checkpoint kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytosine Nucleotides,
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/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2536-44
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15709766-Animals,
pubmed-meshheading:15709766-Casein Kinase I,
pubmed-meshheading:15709766-Casein Kinase II,
pubmed-meshheading:15709766-Cell Line,
pubmed-meshheading:15709766-Consensus Sequence,
pubmed-meshheading:15709766-Cytosine Nucleotides,
pubmed-meshheading:15709766-DNA Damage,
pubmed-meshheading:15709766-DNA-Activated Protein Kinase,
pubmed-meshheading:15709766-DNA-Binding Proteins,
pubmed-meshheading:15709766-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:15709766-Humans,
pubmed-meshheading:15709766-Nuclear Proteins,
pubmed-meshheading:15709766-Nucleic Acid Conformation,
pubmed-meshheading:15709766-Peptide Fragments,
pubmed-meshheading:15709766-Phosphoprotein Phosphatases,
pubmed-meshheading:15709766-Phosphorylation,
pubmed-meshheading:15709766-Protein Kinase C,
pubmed-meshheading:15709766-Protein Kinases,
pubmed-meshheading:15709766-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15709766-Serine,
pubmed-meshheading:15709766-Spodoptera,
pubmed-meshheading:15709766-Tumor Suppressor Protein p53
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pubmed:year |
2005
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pubmed:articleTitle |
Modulation of p53 binding to Holliday junctions and 3-cytosine bulges by phosphorylation events.
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pubmed:affiliation |
Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, 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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