Further characterisation of the p53 responsive element - Identification of new candidate genes for trans-activation by p53
Further characterisation of the p53 responsive element - Identification of new candidate genes for trans-activation by p53
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DOI：
10.1038/sj.onc.1200804
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发表时间：
1997-01-09
期刊：
影响因子：
8
通讯作者：
May, E
中科院分区：
文献类型：
--
作者：
Bourdon, JC;DeguinChambon, V;May, E
已知p53蛋白通过特异性结合包含两个十聚体类型的共有序列：PuPuPuCA/TT/AGPyPyPy，反式激活许多基因。为了发现新的p53反式激活基因，我们定义了一套计算机搜索p53反应元件的标准。根据实验数据，我们提出了一个由El-Deiry共有序列的两个十聚体和两个额外的十聚体组成的扩展共有序列，El-Deiry共有序列的两个十聚体最多可以有3bp的替换，以及对于每个额外的十聚体，除了当El-Deiry共有序列的两个十聚体是邻接的时。在这种情况下，允许每个额外的十聚体在中值C和G之间带有一个碱基插入或缺失，通过鉴定IGF-BP 3基因启动子区域内新的p53应答元件的存在来验证这组标准，该新的p53应答元件的功能意义得到验证，通过对HOVERGEN数据库中的7785个基因序列进行分析，从癌基因、激酶、蛋白酶和结构蛋白中筛选出55个新基因，其中6个基因在多个物种中被检索到
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