敲除 Sam68 基因导致白血病细胞系细胞生长迟缓和 G2/M 期延长

RNA 结合蛋白 Sam68 是细胞有丝分裂期 Src 酪氨酸磷酸化的靶蛋白 . 尽管确切机制尚不清楚，一些人还是认为 Sam68 可通过调控 RNA 的代谢参与细胞周期调控 . 利用基因打靶技术，在 DT40 细胞分离出 Sam68 基因缺失的细胞系 . 利用该细胞系，进行 Sam68 的功能解析 . 与野生型细胞系相比， Sam68 基因缺失细胞表现出明显的生长速度迟缓 . 通过细胞周期研究揭示 , 这些细胞生长速度延迟是由于细胞周期中的 G2/M 期延长 . 因为参与细胞周期 G2/M 期调控的周期因子 Cdc2 激酶的活性没有改变，所以提示 Sam68 不依赖于 Cdc2 激酶的活性参与细胞周期中 G2/M 期调控 .

Knock Out of Sam68 Induces Retardation of the G2-M Phase Progression and Decreased Growth in Leukemia Cell Line

Sam68, a nuclear RNA binding protein, is the Src mitotic target and specifically tyrosine phosphorylated during mitosis. It has also been demonstrated to associate with various signal transduction molecules, thereby raising the possibility of its role in cell cycle control as a modulator of the signal transduction and activation of RNA metabolism. To elucidate the physiological function, a Sam68-deficient cell line was isolated from the chicken DT40 cell line by gene disruption. The Sam68 deficient cells exhibited markedly decreased growth, and forced expression of chicken Sam68 cDNA in the mutant cells restored the cell growth. Cell cycle analysis revealed that the growth retardation was due to elongation of the G2-M phase, however, the kinase activity associated with Cdc2 remained unaltered. The results indicate that Sam68 may play a critical role in G2-M progression in a manner independent of the control of cyclin/Cdc2 kinase activity.