Source:http://linkedlifedata.com/resource/pubmed/id/14572899
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2003-10-23
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pubmed:abstractText |
The cyclin kinase inhibitor p21 associates with and inhibits cyclin-CDKs to retard the progress of the cell cycle in response to DNA damage. The recognition sites for cyclin binding on the various cell cycle-related molecules have been identified as RXL motifs. In the case of p21, the dependence of the Cy1 (18CRRL) or Cy2 (154KRRL) motifs on cyclin E, but not on cyclin A has been demonstrated by in vitro experiments. In this study, to clarify the mechanism of p21 association with cyclin A, we constructed a p21 expression system in mammalian cells. After transfection with an expression vector containing cDNA of various p21-mutants, cells were irradiated with 10 Gy of gamma-rays to introduce DNA damage, followed by quantification of the p21-cyclin A association. The p21-mutant constructs were single or multiple deletions in Cy1, Cy2, and the CDK2 binding region, and a nonphosphorylatable alanine mutant of the C-terminal phosphorylation site. We demonstrated that the association of p21 and cyclin A in response to gamma-irradiation requires the CDK binding region, 49-71 aa, but not the Cy motifs. We believe the mechanism by which p21 inhibits cyclin-CDKs is distinct in each phase of the cell cycle. Furthermore, the increase in the association of p21 and cyclin A was not correlated with the levels of p21. This suggests that DNA damage triggers a signal to the p21 region between 21 and 96 aa to allow cyclin A association.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
1642
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
163-71
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14572899-Alanine,
pubmed-meshheading:14572899-Amino Acid Motifs,
pubmed-meshheading:14572899-Binding Sites,
pubmed-meshheading:14572899-CDC2-CDC28 Kinases,
pubmed-meshheading:14572899-Cell Line, Tumor,
pubmed-meshheading:14572899-Cyclin A,
pubmed-meshheading:14572899-Cyclin-Dependent Kinase 2,
pubmed-meshheading:14572899-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:14572899-Cyclins,
pubmed-meshheading:14572899-Gamma Rays,
pubmed-meshheading:14572899-Humans,
pubmed-meshheading:14572899-Phosphorylation,
pubmed-meshheading:14572899-Precipitin Tests,
pubmed-meshheading:14572899-Protein Binding,
pubmed-meshheading:14572899-Sequence Deletion
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pubmed:year |
2003
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pubmed:articleTitle |
The association of cyclin A and cyclin kinase inhibitor p21 in response to gamma-irradiation requires the CDK2 binding region, but not the Cy motif.
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pubmed:affiliation |
Department of Clinical Pathology, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8666, Japan. kfukuchi@med.showa-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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