Cyclins A and B1 in the human cell cycle.
Cyclins are a family of proteins involved in the regulation of the eukaryotic cell cycle. The first cyclins to be isolated were the A- and B-type cyclins and we have been studying their behaviour in human somatic cells. The levels of both cyclin A and B1 are regulated transcriptionally as well as post-translationally; both are rapidly and specifically degraded in mitosis. Cyclin A synthesis commences at the start of S phase and the protein is predominantly nuclear, whereas cyclin B1 appears during S phase and is primarily cytoplasmic. Cyclin B1 moves into the nucleus just at the start of mitosis and associates with condensed chromosomes and the mitotic spindle. Both cyclin A and cyclin B1 bind to and activate a protein serine/threonine kinase subunit; cyclin A associates with p33cdk2 and with p34cdc2, whereas cyclin B1 seems to bind exclusively to p34cdc2. Cyclin A-associated kinase activity appears much earlier in the cell cycle than that of cyclin B1, which appears only at the G2 to M transition. Therefore cyclin A may play a role in the events of S phase as well as G2 and M phases. Cyclin A forms a cell cycle-dependent complex with p33cdk2 and the transcription factor E2F, although the function of this complex is not yet clear. We conclude that cyclins A and B1 may differentially regulate the cell cycle in several ways. They form complexes with distinct protein kinases and these complexes are active at different times in the cell cycle; they form distinct multiprotein complexes, such as with the transcription factor E2F; and they are localized to different parts of the cell where different substrates will be available to them.
Pines
J
J
Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, CA 92186-5800.
Hunter
T
T
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000502:physiology*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment
D016213:Cyclins; D012333:RNA, Messenger; D011494:Protein Kinases