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生长抑制因子p53蛋白与细胞周期调节磷酸酶cdc25C的结合。

Binding of the growth suppressor p53 protein to the cell cycle regulator phosphatase cdc25C.

作者信息

Rief N, Herges H, Prowald A, Götz C, Montenarh M

机构信息

Medical Biochemistry and Molecular Biology, University of the Saarland, D-66421 Homburg, Germany.

出版信息

Int J Oncol. 2000 Jul;17(1):189-95. doi: 10.3892/ijo.17.1.189.

Abstract

Human p53 is a growth suppressor which not only functions in mammalian cells but also in fission yeast. It was previously shown that the cell cycle regulating phosphatase cdc25C suppresses the p53 induced growth arrest in fission yeast. In the present study we analysed the mechanism of this suppression. We found that cdc25C directly interacts with p53. By using different deletion mutants the binding region was narrowed down on the polypeptide chain of p53 to amino acids 287-340. To test the functional significance we analysed the effect of this interaction on the DNA binding activity of p53. As shown by band shift experiments binding of cdc25C to p53 does not modify the DNA binding activity of p53. Our data suggest that the observed suppression of the p53 induced growth arrest by cdc25C might be achieved by direct binding of cdc25C to the C-terminus of p53.

摘要

人类p53是一种生长抑制因子,它不仅在哺乳动物细胞中发挥作用,也在裂殖酵母中发挥作用。先前的研究表明,细胞周期调节磷酸酶cdc25C可抑制裂殖酵母中p53诱导的生长停滞。在本研究中,我们分析了这种抑制作用的机制。我们发现cdc25C直接与p53相互作用。通过使用不同的缺失突变体,将p53多肽链上的结合区域缩小至氨基酸287 - 340。为了测试其功能意义,我们分析了这种相互作用对p53 DNA结合活性的影响。如凝胶迁移实验所示,cdc25C与p53的结合不会改变p53的DNA结合活性。我们的数据表明,观察到的cdc25C对p53诱导的生长停滞的抑制作用可能是通过cdc25C直接结合到p53的C末端实现的。

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