Cyclin A is required at two points in the human cell cycle.
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.
Pagano
M
M
Differentiation, Programme European Molecular Biology Laboratory, Heidelberg, Germany.
Pepperkok
R
R
Verde
F
F
Ansorge
W
W
Draetta
G
G
D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008845:Microinjections; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D010957:Plasmids; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism
D017456:Adenovirus Early Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D010770:Phosphotransferases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases