D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA.
Human cyclin D1 has been associated with a wide variety of proliferative diseases but its biochemical role is unknown. In diploid fibroblasts we find that cyclin D1 is complexed with many other cellular proteins. Among them are protein kinase catalytic subunits CDK2, CDK4 (previously called PSK-J3), and CDK5 (also called PSSALRE). In addition, polypeptides of 21 kd and 36 kd are identified in association with cyclin D1. We show that the 36 kd protein is the proliferating cell nuclear antigen, PCNA. Cyclin D3 also associates with multiple protein kinases, p21 and PCNA. It is proposed that there exists a quaternary complex of D cyclin, CDK, PCNA, and p21 and that many combinatorial variations (cyclin D1, D3, CDK2, 4, and 5) may assemble in vivo. These findings link a human putative G1 cyclin that is associated with oncogenesis with a well-characterized DNA replication and repair factor.
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
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Xiong
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Zhang
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Beach
D000595:Amino Acid Sequence; D019938:Cyclin D1; D056743:Cyclin D3; D016213:Cyclins / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D015513:Oncogene Proteins / Q000737:chemistry*; D018809:Proliferating Cell Nuclear Antigen; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry*
C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D011494:Protein Kinases