Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
We have used immunofluorescence staining to study the subcellular distribution of cyclin A and B1 during the somatic cell cycle. In both primary human fibroblasts and in epithelial tumor cells, we find that cyclin A is predominantly nuclear from S phase onwards. Cyclin A may associated with condensing chromosomes in prophase, but is not associated with condensed chromosomes in metaphase. By contrast, cyclin B1 accumulates in the cytoplasm of interphase cells and only enters the nucleus at the beginning of mitosis, before nuclear lamina breakdown. In mitotic cells, cyclin B1 associates with condensed chromosomes in prophase and metaphase, and with the mitotic apparatus. Cyclin A is degraded during metaphase and cyclin B1 is precipitously destroyed at the metaphase----anaphase transition. Cell fractionation and immunoprecipitation studies showed that both cyclin A and cyclin B1 are associated with PSTAIRE-containing proteins. The nuclear, but not the cytoplasmic form, of cyclin A is associated with a 33-kD PSTAIRE-containing protein. Cyclin B1 is associated with p34cdc2 in the cytoplasm. Thus we propose that the different localization of cyclin A and cyclin B1 in the cell cycle could be the means by which the two types of mitotic cyclin confer substrate specificity upon their associated PSTAIRE-containing protein kinase subunit.
Pines
J
J
Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186-5800.
Hunter
T
T
D001692:Biological Transport; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002451:Cell Compartmentation; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D006801:Humans; D008677:Metaphase; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
D016213:Cyclins; D000939:Epitopes; D009687:Nuclear Proteins; D016203:CDC2 Protein Kinase