Horton L E, Templeton D J
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Oncogene. 1997 Jan 30;14(4):491-8. doi: 10.1038/sj.onc.1200851.
The cyclins and their catalytic partners, the Cyclin Dependent Kinases (CDKs), are essential for progression through the cell cycle. Cyclin/kinase complexes containing cyclins A or E are active primarily in late G1 to S phase and both have been shown to phosphorylate histone H1 and the retinoblastoma gene product (pRb) in vitro. Despite these similarities, cyclins A and E display differences in CDK activation and substrate specificity. We find that in vitro, cyclin E/CDK2 and cyclin A/CDK2 phosphorylate histone H1 similarly but only cyclin A/CDK2 phosphorylates lamin B. While both cyclin A and cyclin E bind CDK1 efficiently, only cyclin A activates CDK1 kinase activity. Using chimeric proteins between cyclins A and E we find that both the cyclin box and C-terminus of cyclins A and E are required for CDK binding, activation and targeting of substrate specificity.
细胞周期蛋白及其催化伴侣，即细胞周期蛋白依赖性激酶（CDK），对于细胞周期的进程至关重要。含有细胞周期蛋白A或E的细胞周期蛋白/激酶复合物主要在G1晚期至S期具有活性，并且两者在体外均已显示出可磷酸化组蛋白H1和视网膜母细胞瘤基因产物（pRb）。尽管存在这些相似之处，但细胞周期蛋白A和E在CDK激活和底物特异性方面存在差异。我们发现在体外，细胞周期蛋白E/CDK2和细胞周期蛋白A/CDK2对组蛋白H1的磷酸化作用相似，但只有细胞周期蛋白A/CDK2可磷酸化核纤层蛋白B。虽然细胞周期蛋白A和细胞周期蛋白E都能有效地结合CDK1，但只有细胞周期蛋白A能激活CDK1激酶活性。利用细胞周期蛋白A和E之间的嵌合蛋白，我们发现细胞周期蛋白A和E的细胞周期蛋白框和C末端对于CDK结合、激活以及底物特异性靶向都是必需的。
