Pusch O, Bernaschek G, Eilers M, Hengstschläger M
Obstetrics and Gynecology, University of Vienna, Department of Prenatal Diagnosis and Therapy, Austria.
Oncogene. 1997 Aug 7;15(6):649-56. doi: 10.1038/sj.onc.1201236.
Proto-oncogenes like c-myc are thought to control exit from the cell cycle rather than progression through the cell cycle itself. We now present a different view of Myc function. Exponentially growing Rat1-MycER fibroblasts were size-fractionated by centrifugal elutriation. In these cells, activation of cyclin E- and cyclin A-dependent kinases, degradation of p27, hyperphosphorylation of retinoblastoma protein and activation of E2F occur sequentially at specific cell sizes. Upon activation of Myc, however, these transitions all occur simultaneously in small cells immediately after exit from mitosis. In contrast, Myc has no discernible effect on the cell size at which DNA replication is initiated. These data show first that Myc controls the activity of G1 cyclin-dependent kinases independently from the transition between quiescence and proliferation and from any effect on cell growth in size. These data also provide evidence of at least one dominant mechanism besides activation of E2F and of cyclin E/cdk2 kinase, which prevents DNA replication unless a critical cell size has been reached.
像c-myc这样的原癌基因被认为是控制细胞周期的退出，而不是细胞周期本身的进程。我们现在提出了一种关于Myc功能的不同观点。通过离心淘析对指数生长的Rat1-MycER成纤维细胞进行大小分级。在这些细胞中，细胞周期蛋白E和细胞周期蛋白A依赖性激酶的激活、p27的降解、视网膜母细胞瘤蛋白的过度磷酸化以及E2F的激活在特定细胞大小时依次发生。然而，在Myc激活后，这些转变在有丝分裂退出后立即在小细胞中同时发生。相比之下，Myc对启动DNA复制的细胞大小没有明显影响。这些数据首先表明，Myc独立于静止与增殖之间的转变以及对细胞大小生长的任何影响来控制G1期细胞周期蛋白依赖性激酶的活性。这些数据还提供了证据，表明除了E2F激活和细胞周期蛋白E/周期蛋白依赖性激酶2激酶激活之外，至少还有一种主要机制，该机制可防止DNA复制，除非达到临界细胞大小。
