Cyclin A Is Required at Two Points in the Human Cell Cycle

EMBO J. 1992 Mar;11(3):961-71.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Early Proteins
  • Amino Acid Sequence
  • Blotting, Western
  • CDC2 Protein Kinase / metabolism
  • CDC2-CDC28 Kinases*
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Cycle*
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Cyclins / genetics
  • Cyclins / immunology
  • Cyclins / metabolism*
  • DNA Replication
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Fluorescent Antibody Technique
  • Gene Expression
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Microinjections
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / metabolism
  • Phosphotransferases / metabolism
  • Plasmids
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / metabolism

Substances

  • Adenovirus Early Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Oncogene Proteins, Viral
  • Recombinant Proteins
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Phosphotransferases
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases