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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1994-4-22
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pubmed:abstractText |
gamma-Irradiation of human diploid fibroblasts in the G1 interval caused arrest of the cell cycle prior to S phase. This cell cycle block was correlated with a lack of activation of both cyclin E-Cyclin-dependent kinase 2 (Cdk2) and cyclin A-Cdk2 kinases and depended on wild-type p53. Although the accumulation of cyclin A was strongly inhibited in gamma-irradiated cells, cyclin E accumulated and bound Cdk2 at normal levels but remained in an inactive state. We found that both whole-cell lysates and inactive cyclin E-Cdk2 complexes prepared from irradiated cells contained an activity capable of inactivating cyclin E-Cdk2 complexes. The protein responsible for this activity was shown to be p21CIP1/WAF1, recently described as a p53-inducible Cdk inhibitor. Our data suggest a model in which ionizing radiation confers G1 arrest via the p53-mediated induction of a Cdk inhibitor 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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1013-23
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8137420-Base Sequence,
pubmed-meshheading:8137420-Cells, Cultured,
pubmed-meshheading:8137420-Cyclin D1,
pubmed-meshheading:8137420-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:8137420-Cyclins,
pubmed-meshheading:8137420-Enzyme Activation,
pubmed-meshheading:8137420-Fibroblasts,
pubmed-meshheading:8137420-G1 Phase,
pubmed-meshheading:8137420-Gamma Rays,
pubmed-meshheading:8137420-Humans,
pubmed-meshheading:8137420-Male,
pubmed-meshheading:8137420-Molecular Sequence Data,
pubmed-meshheading:8137420-Oncogene Proteins,
pubmed-meshheading:8137420-Protein Kinase Inhibitors,
pubmed-meshheading:8137420-Protein Kinases,
pubmed-meshheading:8137420-Retinoblastoma Protein,
pubmed-meshheading:8137420-Tumor Suppressor Protein p53
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pubmed:year |
1994
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pubmed:articleTitle |
p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.
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pubmed:affiliation |
Department of Molecular Biology MB-7, Scripps Research Institute, La Jolla, California 92037.
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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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