Bourdon J C, Deguin-Chambon V, Lelong J C, Dessen P, May P, Debuire B, May E
UMR 217 du CNRS, Laboratoire de Cancérogenèse Moléculaire, CEA, Fontenay-aux-Roses, France.
Oncogene. 1997 Jan 9;14(1):85-94. doi: 10.1038/sj.onc.1200804.
The p53 protein is known to trans-activate a number of genes by specific binding to a consensus sequence containing two decamers of the type: PuPuPuCA/TT/AGPyPyPy. In order to identify new p53 trans-activated genes, we defined a set of criteria for computer search of p53-responsive elements. Based on experimental data, we proposed an extended consensus sequence composed of the two decamers of the El-Deiry consensus sequence flanked by two additional ones. A maximum of 3 bp substitutions was accepted for the two decamers of the El-Deiry consensus sequence, as well as for each additional decamer, except when the two decamers of the El-Deiry consensus sequence are contiguous. In this case, each additional decamer is allowed to bear one base insertion or deletion between the median C and G. This set of criteria was validated by identifying within the promoter region of the IGF-BP3 gene the existence of a novel p53-responsive element whose functional significance was verified. By limiting our computer search to Vertebrate genes involved in cell cycle regulation, cellular adhesion or metastatic processes and to gene families most often found in HOVERGEN database, 7785 gene sequences were first analysed. Among the oncogenes, kinases, proteases and structural proteins, 55 new genes were selected; six of them were retrieved in more than one species.
已知p53蛋白通过与包含两个十聚体的共有序列特异性结合来反式激活许多基因，该十聚体类型为：PuPuPuCA/TT/AGPyPyPy。为了鉴定新的p53反式激活基因，我们定义了一套用于计算机搜索p53反应元件的标准。基于实验数据，我们提出了一个扩展的共有序列，它由El-Deiry共有序列的两个十聚体两侧各加两个十聚体组成。对于El-Deiry共有序列的两个十聚体以及每个额外的十聚体，最多接受3个碱基替换，但当El-Deiry共有序列的两个十聚体相邻时除外。在这种情况下，每个额外的十聚体在中间的C和G之间允许有一个碱基插入或缺失。通过在IGF-BP3基因的启动子区域内鉴定出一个新的p53反应元件的存在并验证其功能意义，这套标准得到了验证。通过将我们的计算机搜索限制在参与细胞周期调控、细胞黏附或转移过程的脊椎动物基因以及HOVERGEN数据库中最常出现的基因家族，首先分析了7785个基因序列。在癌基因、激酶、蛋白酶和结构蛋白中，选择了55个新基因；其中6个在不止一个物种中被检索到。
