The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function
The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function
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DOI：
10.1074/jbc.m302902200
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发表时间：
2003-08-08
影响因子：
4.8
通讯作者：
Schneider, C
中科院分区：
文献类型：
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作者：
Monte, M;Benetti, R;Schneider, C
GTSE-1（G（2）and S phase-expressed-1）蛋白在细胞周期的S和G（2）期特异性表达。它主要定位于微管，并且当过度表达时延迟G（2）到M的转变。在这里，我们报告，人GTSE-1（hGTSE-1）蛋白可以负调控p53反式激活功能，蛋白水平，和p53依赖性细胞凋亡。我们确定了p53的C-末端调控结构域和hGTSE-1的C-末端区域之间的物理相互作用，这是必要的，足以下调p53活性。此外，我们提供的证据表明，hGTSE-1是能够控制p53功能的细胞周期依赖性的方式。通过小干扰RNA敲低hGTSE-1导致S/G（2）特异性p53水平升高，以及细胞对DNA损伤诱导的细胞凋亡的敏感性。总之，这项工作表明，在S期和G（2）期DNA损伤后，hGTSE-1通过调节p53功能在细胞凋亡控制中发挥生理作用。
GTSE-1 (G(2) and S phase-expressed-1) protein is specifically expressed during S and G(2) phases of the cell cycle. It is mainly localized to the microtubules and when overexpressed delays the G(2) to M transition. Here we report that human GTSE-1 (hGTSE-1) protein can negatively regulate p53 transactivation function, protein levels, and p53-dependent apoptosis. We identified a physical interaction between the C-terminal regulatory domain of p53 and the C-terminal region of hGTSE-1 that is necessary and sufficient to down-regulate p53 activity. Furthermore, we provide evidence that hGTSE-1 is able to control p53 function in a cell cycle-dependent fashion. hGTSE-1 knock-down by small interfering RNA resulted in a S/G(2)-specific increase of p53 levels as well as cell sensitization to DNA damage-induced apoptosis during these phases of the cell cycle. Altogether, this work suggests a physiological role of hGTSE-1 in apoptosis control after DNA damage during S and G(2) phases through regulation of p53 function.