Yang R, Müller C, Huynh V, Fung Y K, Yee A S, Koeffler H P
Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA.
Mol Cell Biol. 1999 Mar;19(3):2400-7. doi: 10.1128/MCB.19.3.2400.
Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.
人细胞周期蛋白A1是一种新发现的细胞周期蛋白，在睾丸中表达，被认为在减数分裂细胞周期中发挥作用。在此，我们表明人细胞周期蛋白A1的表达及其相关激酶活性在有丝分裂细胞周期中受到调控。在骨肉瘤细胞系MG63中，细胞周期蛋白A1的mRNA和蛋白在G0期细胞中含量极低。它们在细胞周期进程中增加，并在S期和G2/M期达到最高水平。此外，细胞周期蛋白A1相关的组蛋白H1激酶活性在G2/M期达到峰值。我们报道细胞周期蛋白A1可与重要的细胞周期调节因子结合：Rb蛋白家族、转录因子E2F-1以及p21蛋白家族。当细胞周期蛋白A1与CDK2形成复合物时，其与E2F-1的体外相互作用大大增强。在几种细胞系的体内实验中观察到细胞周期蛋白A1与Rb和E2F-1的结合。当细胞周期蛋白A1与CDK2在sf9昆虫细胞中共表达时，CDK2-细胞周期蛋白A1复合物对组蛋白H1、E2F-1以及Rb蛋白家族具有激酶活性。我们的结果表明，Rb蛋白家族和E2F-1可能是细胞周期蛋白A1相关激酶磷酸化的重要靶点。细胞周期蛋白A1可能在某些细胞的有丝分裂细胞周期中发挥作用。
