14-3-3σ is a p53-regulated inhibitor of G2/M progression
14-3-3σ is a p53-regulated inhibitor of G2/M progression
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DOI：
10.1016/s1097-2765(00)80002-7
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发表时间：
1997-12-01
期刊：
影响因子：
16
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Hermeking, H;Lengauer, C;Vogelstein, B
结直肠癌 (CRC) 细胞暴露于电离辐射会导致细胞周期停滞在 G1 和 G2 期。 G1 停滞是由于 p53 介导的细胞周期蛋白依赖性激酶抑制剂 p21 (WAF1/CIP1/SDI1) 的诱导，但 G2 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 14-3-3 sigma 受到伽马射线照射和其他 DNA 损伤剂的强烈诱导。 14-3-3 sigma 的诱导是由位于其转录起始位点上游 1.8 kb 的 p53 响应元件介导的。将 14-3-3 σ 外源引入循环细胞会导致 G2 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，这些结果记录了 G2/M 控制的分子机制，该机制在整个真核进化过程中都是保守的，并在人类细胞中受到 p53 的调节。
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 p21(WAF1/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 14-3-3 sigma is strongly induced by gamma irradiation and other DNA-damaging agents. The induction of 14-3-3 sigma is mediated by a p53-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3 sigma 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.