Leone G, DeGregori J, Jakoi L, Cook J G, Nevins J R
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6626-31. doi: 10.1073/pnas.96.12.6626.
A considerable body of evidence points to a role for both cyclin E/cyclin-dependent kinase (cdk)2 activity and E2F transcription activity in the induction of S phase. We show that overexpression of cyclin E/cdk2 in quiescent cells induces S phase, that this coincides with an induction of E2F activity, and that coexpression of E2F enhances the cyclin E/cdk2-mediated induction of S phase. Likewise, E2F overexpression can induce S phase and does so in the apparent absence of cyclin E/cdk2 activity. In addition, although the inhibition of cyclin E/cdk2 activity blocks the induction of S phase after growth stimulation of normal mouse embryo fibroblasts, inhibition of cyclin E/cdk2 does not block S phase induction in Rb-/- cells where E2F activity is deregulated. These results point to the important roles for E2F and cyclin E/cdk2 in the induction of S phase. Moreover, the nature of the E2F targets and the suspected targets for cyclin E/cdk2 suggests a potential molecular mechanism for the collaborative action of cyclin E/cdk2 and E2F in the induction of S phase.
大量证据表明，细胞周期蛋白E/细胞周期蛋白依赖性激酶（cdk）2活性和E2F转录活性在S期诱导过程中均发挥作用。我们发现，在静止细胞中过表达细胞周期蛋白E/cdk2可诱导S期，这与E2F活性的诱导同时发生，并且E2F的共表达增强了细胞周期蛋白E/cdk2介导的S期诱导。同样，E2F过表达也可诱导S期，且在明显缺乏细胞周期蛋白E/cdk2活性的情况下也能如此。此外，尽管抑制细胞周期蛋白E/cdk2活性可阻断正常小鼠胚胎成纤维细胞生长刺激后S期的诱导，但在E2F活性失调的Rb-/-细胞中，抑制细胞周期蛋白E/cdk2并不能阻断S期诱导。这些结果表明E2F和细胞周期蛋白E/cdk2在S期诱导中具有重要作用。此外，E2F靶标的性质以及细胞周期蛋白E/cdk2的疑似靶标提示了细胞周期蛋白E/cdk2和E2F在S期诱导中协同作用的潜在分子机制。
