Abstract
Cyclins play a fundamental role in regulating cell cycle events in all eukaryotic cells. The human cyclin A gene was identified as the site of integration of hepatitis B virus in a hepatocarcinoma cell line; in addition, cyclin A is associated with the E2F transcription factor in a complex which is dissociated by the E1A oncogene product. Such findings suggest that cyclin A is a target for oncogenic signals. We have now found that DNA synthesis and entry into mitosis are inhibited in human cells microinjected with anti-cyclin A antibodies at distinct times. Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenovirus Early Proteins
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Amino Acid Sequence
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Blotting, Western
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CDC2 Protein Kinase / metabolism
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CDC2-CDC28 Kinases*
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Cycle*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases*
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Cyclins / genetics
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Cyclins / immunology
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Cyclins / metabolism*
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DNA Replication
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DNA-Binding Proteins*
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E2F Transcription Factors
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Fluorescent Antibody Technique
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Gene Expression
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HeLa Cells
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Humans
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Immunohistochemistry
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Kinetics
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Microinjections
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Molecular Sequence Data
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Oncogene Proteins, Viral / metabolism
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Phosphotransferases / metabolism
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Plasmids
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors / metabolism
Substances
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Adenovirus Early Proteins
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Carrier Proteins
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Cell Cycle Proteins
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Cyclins
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DNA-Binding Proteins
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E2F Transcription Factors
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Oncogene Proteins, Viral
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Recombinant Proteins
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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Phosphotransferases
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Protein Kinases
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases