Zariwala M, Liu J, Xiong Y
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599-3280, USA.
Oncogene. 1998 Nov 26;17(21):2787-98. doi: 10.1038/sj.onc.1202505.
G1 cyclin E controls the initiation of DNA synthesis by activating CDK2, and abnormally high levels of cyclin E expression have frequently been observed in human cancers. We have isolated a novel human cyclin, cyclin E2, that contains significant homology to cyclin E. Cyclin E2 specifically interacts with CDK inhibitors of the CIP/KIP family and activates both CDK2 and CDK3. The expression of cyclin E2 mRNA oscillates periodically throughout the cell cycle, peaking at the G1/S transition, and exhibits a pattern of tissue specificity distinct from that of cyclin E1. Cyclin E2 encodes a short lived protein whose turnover is most likely governed by the proteasome pathway and is regulated by phosphorylation on a conserved Thr-392 residue. Expression of the viral E6 oncoprotein in normal human fibroblasts increases the steady state level of cyclin E2, but not cyclin E1, while expression of the E7 oncoprotein upregulates both. These data suggest that the expression of these two G1 E-type cyclins may be similarly regulated by the pRb function, but distinctly by the p53 activity.
G1期细胞周期蛋白E通过激活CDK2来控制DNA合成的起始，而在人类癌症中经常观察到细胞周期蛋白E表达水平异常升高。我们分离出了一种新型人类细胞周期蛋白——细胞周期蛋白E2，它与细胞周期蛋白E具有显著的同源性。细胞周期蛋白E2特异性地与CIP/KIP家族的CDK抑制剂相互作用，并激活CDK2和CDK3。细胞周期蛋白E2 mRNA的表达在整个细胞周期中周期性振荡，在G1/S期转换时达到峰值，并且呈现出与细胞周期蛋白E1不同的组织特异性模式。细胞周期蛋白E2编码一种寿命较短的蛋白质，其周转很可能受蛋白酶体途径调控，并受保守的苏氨酸-392残基磷酸化的调节。在正常人成纤维细胞中病毒E6癌蛋白的表达增加了细胞周期蛋白E2的稳态水平，但不影响细胞周期蛋白E1，而E7癌蛋白的表达则上调了两者。这些数据表明，这两种G1期E型细胞周期蛋白的表达可能受pRb功能类似的调控，但受p53活性的调控则明显不同。
