Abstract
Introduction of the E1A early region of the human adenovirus type 5 impairs the ability of mammalian cells to arrest the cell cycle at G1/S after damage. Two-parameter fluorescent-activated cell sorting (FACS) with iododeoxyuridine revealed the radiation-induced G1/S arrest in rat embryo fibroblasts transformed with the complementing E1A + E1B-19 kDa oncogenes. This was due to selective inhibition of CycIE/Cdk2-associated kinase activity, while activities of type 2 kinase and of CyclA/Cdk2 complexes remained unchanged. The inhibitor of G1-phase cyclin kinases, p21/Waf1, was accumulated and interacted with target kinases both in normal and in transformed cells after irradiation. As shown by immunoprecipitation, p21/Waf1 formed complexes with the E1A on coproducts in the transformants, which possibly accounted for its functional inactivation. Kinase modification in cyclin-kinase complexes was assumed to play a key role in regulation of cyclin-dependent kinases in the transformants with inactivated p21/Waf1.
MeSH terms
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Adenovirus E1A Proteins / genetics*
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Adenovirus E1A Proteins / metabolism
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Adenovirus E1A Proteins / radiation effects
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Adenovirus E1B Proteins / genetics*
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Adenovirus E1B Proteins / metabolism*
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Adenovirus E1B Proteins / radiation effects
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Animals
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CDC2-CDC28 Kinases*
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Cell Cycle / genetics*
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Cell Cycle / radiation effects*
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Cells, Cultured
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Cyclin A / metabolism
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Cyclin A / radiation effects
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Cyclin E / metabolism
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Cyclin E / radiation effects
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases / metabolism
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Cyclin-Dependent Kinases / radiation effects
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Cyclins / metabolism
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Embryo, Mammalian / cytology
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Fibroblasts / cytology
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Fibroblasts / radiation effects
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Gamma Rays
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Precipitin Tests
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / radiation effects
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Proto-Oncogene Proteins*
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Rats
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Transfection
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Protein p53 / radiation effects
Substances
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Adenovirus E1A Proteins
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Adenovirus E1B Proteins
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Cdkn1a protein, rat
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Cyclin A
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Cyclin E
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Proto-Oncogene Proteins
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Tumor Suppressor Protein p53
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cdk2 protein, rat
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Cdk4 protein, rat
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases