Anchorage independent cell cycle start

成纤维细胞需要锚定在细胞外基质上才能从G1期过渡到S期，但在致癌转化后不再需要锚定。我们报道，激活复制起始点所必需的Cdc6蛋白需要锚定或致癌刺激才能执行。在锚定缺失的情况下，尽管e2f依赖性启动子被强制激活，但在大鼠成纤维细胞中，Cdc6的转录和转录后表达都被关闭。然而，用致癌生长因子刺激该细胞抑制了这种关闭，同时激活了Cdk2和Cdk6/4，从而超越了G1-S过渡的锚定要求，从而使细胞能够进行锚定不依赖的S期进入。强制表达Cdc6的分析表明，G1周期蛋白依赖性激酶和Cdc6是通过锚定缺失限制G1- s转变的主要细胞周期靶点。

Fibroblasts need anchorage to extracellular matrix to transit from G1 to S phase, but no longer after oncogenic transformation. We report that Cdc6 protein essential for the activation of replication origins requires anchorage or oncogenic stimulation for its execution. Upon anchorage loss, Cdc6 expression is shut of both transcriptionally and post-transcriptionally in a rat fibroblast despite enforced activation of E2F-dependent promoters. However, stimulation of this cell with oncogenic growth factors suppresses this shutoff and concurrently activates Cdk2 and Cdk6/4, thereby overriding the anchorage requirement for the G1-S transition and consequently enabling cells to perform anchorage-independent S phase entry. Analysis with enforced expression of Cdc6 indicates that the G1 cyclin-dependent kinases and Cdc6 constitute major cell cycle targets for the restriction of the G1-S transition by anchorage loss.