Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G
Differentiation, Programme European Molecular Biology Laboratory, Heidelberg, Germany.
EMBO J. 1992 Mar;11(3):961-71. doi: 10.1002/j.1460-2075.1992.tb05135.x.
Cyclins play a fundamental role in regulating cell cycle events in all eukaryotic cells. The human cyclin A gene was identified as the site of integration of hepatitis B virus in a hepatocarcinoma cell line; in addition, cyclin A is associated with the E2F transcription factor in a complex which is dissociated by the E1A oncogene product. Such findings suggest that cyclin A is a target for oncogenic signals. We have now found that DNA synthesis and entry into mitosis are inhibited in human cells microinjected with anti-cyclin A antibodies at distinct times. Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle.
细胞周期蛋白在所有真核细胞中调节细胞周期事件起着基本作用。人细胞周期蛋白A基因被鉴定为乙型肝炎病毒在肝癌细胞系中的整合位点；此外，细胞周期蛋白A与E2F转录因子在一个复合物中相关联，该复合物被E1A癌基因产物解离。这些发现表明细胞周期蛋白A是致癌信号的靶点。我们现在发现，在不同时间显微注射抗细胞周期蛋白A抗体的人细胞中，DNA合成和进入有丝分裂受到抑制。细胞周期蛋白A与cdk2和cdc2都结合，产生两种不同的细胞周期蛋白A激酶活性，一种出现在S期，另一种出现在G2期。这些结果表明细胞周期蛋白A定义了人类细胞周期的新控制点。
