Department of Therapeutic Programs Development, Regina Elena Cancer Institute, Rome, Italy.
Cancer Cell. 2010 Aug 9;18(2):122-34. doi: 10.1016/j.ccr.2010.05.027.
Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53.
Che-1 是一种 RNA 聚合酶 II 结合蛋白,参与基因转录的调节,并且在响应 DNA 损伤时促进 p53 转录。在这项研究中,我们研究了 Che-1 是否调节突变型 p53 的表达。我们发现 Che-1 在几种癌细胞系中维持突变型 p53 表达是必需的,并且 siRNA 敲低 Che-1 会在体外和体内诱导细胞凋亡。值得注意的是,Che-1 的缺失激活了 DNA 损伤检查点反应,并诱导了 p73 的反式激活。因此,这些发现强调了 Che-1 在表达突变型 p53 的细胞存活中的重要作用。