Hermeking H, Lengauer C, Polyak K, He T C, Zhang L, Thiagalingam S, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland, USA.
Mol Cell. 1997 Dec;1(1):3-11. doi: 10.1016/s1097-2765(00)80002-7.
Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a cell-cycle arrest in G1 and G2. The G1 arrest is due to p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3sigma is strongly induced by gamma irradiation and other DNA-damaging agents. The induction of 14-3-3sigma is mediated by a p53-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3sigma into cycling cells results in a G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, these results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53.
结肠直肠癌（CRC）细胞暴露于电离辐射会导致细胞周期在G1期和G2期停滞。G1期停滞是由于p53介导的细胞周期蛋白依赖性激酶抑制剂p21WAF1/CIP1/SDI1的诱导，但G2期停滞的基础尚不清楚。通过对CRC细胞系中基因表达模式的定量分析，我们发现14-3-3sigma受到γ射线照射和其他DNA损伤剂的强烈诱导。14-3-3sigma的诱导由位于其转录起始位点上游1.8 kb处的p53反应元件介导。将14-3-3sigma外源导入循环细胞会导致G2期停滞。由于裂殖酵母14-3-3同源物rad24和rad25介导类似的检查点效应，这些结果证明了一种在整个真核生物进化过程中保守且在人类细胞中由p53调节的G2/M控制分子机制。
