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rdf:type |
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lifeskim:mentions |
umls-concept:C0079184,
umls-concept:C0079419,
umls-concept:C0205145,
umls-concept:C0205245,
umls-concept:C0220905,
umls-concept:C1514562,
umls-concept:C1522290,
umls-concept:C1549781,
umls-concept:C1707271,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
3
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pubmed:dateCreated |
2000-8-10
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pubmed:abstractText |
Radiation injury to cells enhances C-terminal phosphorylation of p53 at both Ser315 and Ser392 in vivo, suggesting the existence of two cooperating DNA damage-responsive pathways that play a role in stimulating p53-dependent gene expression. Our previous data has shown that cyclin A-cdk2 is the major enzyme responsible for modifying p53 at Ser315 in vivo after irradiation damage and in this report we dissect the mechanism of cyclinA-cdk2 binding to and phosphorylation of p53. Although cyclin B(1)-dependent protein kinases can phosphorylate small peptides containing the Ser315 site, cyclin A-cdk2 does not phosphorylate such small peptides suggesting that additional determinants are required for cyclin A-cdk2 interaction with p53. Peptide competition studies have localized a cyclin A interaction site to a Lys381Lys382Leu383Met384Phe385 sequence within C-terminal negative regulatory domain of human p53. An alanine mutation at any one of four key positions abrogates the efficacy of a synthetic peptide containing this motif as an inhibitor of cyclin A-cdk2 phosphorylation of p53 protein. Single amino acid mutations of full-length p53 protein at Lys382, Leu383, or Phe385 decreases cyclin A-cdk2 dependent phosphorylation at Ser315. Cyclin B(1)-cdk2 complexes are not inhibited by KKLMF motif-containing peptides nor is p53 phosphorylation by cyclin B-cdk2 reduced by mutation of the cyclin A interaction site. These data identifying a KKLMF cyclin A docking site on p53 protein highlight a common cyclin A interaction motif that is shared between the tumour suppressor proteins pRb and p53.
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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/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/histone H1 kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2836
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
300
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
503-18
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10884347-Amino Acid Motifs,
pubmed-meshheading:10884347-Amino Acid Sequence,
pubmed-meshheading:10884347-Amino Acid Substitution,
pubmed-meshheading:10884347-Antibodies,
pubmed-meshheading:10884347-Binding Sites,
pubmed-meshheading:10884347-CDC2-CDC28 Kinases,
pubmed-meshheading:10884347-Cyclin A,
pubmed-meshheading:10884347-Cyclin B,
pubmed-meshheading:10884347-Cyclin B1,
pubmed-meshheading:10884347-Cyclin-Dependent Kinase 2,
pubmed-meshheading:10884347-Cyclin-Dependent Kinases,
pubmed-meshheading:10884347-Histones,
pubmed-meshheading:10884347-Humans,
pubmed-meshheading:10884347-Molecular Sequence Data,
pubmed-meshheading:10884347-Mutation,
pubmed-meshheading:10884347-Peptide Fragments,
pubmed-meshheading:10884347-Phosphorylation,
pubmed-meshheading:10884347-Phosphoserine,
pubmed-meshheading:10884347-Protein Binding,
pubmed-meshheading:10884347-Protein Kinase Inhibitors,
pubmed-meshheading:10884347-Protein Kinases,
pubmed-meshheading:10884347-Protein Structure, Tertiary,
pubmed-meshheading:10884347-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10884347-Recombinant Fusion Proteins,
pubmed-meshheading:10884347-Sequence Alignment,
pubmed-meshheading:10884347-Tumor Cells, Cultured,
pubmed-meshheading:10884347-Tumor Suppressor Protein p53
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pubmed:year |
2000
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pubmed:articleTitle |
The C-terminal regulatory domain of p53 contains a functional docking site for cyclin A.
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pubmed:affiliation |
Department of Molecular and Cellular Pathology, Cancer Research Campaign Laboratories, University of Dundee Medical School, Scotland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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