FURTHER CHARACTERIZATION OF THE P53 RESPONSIVE ELEMENT - IDENTIFICATION OF NEW CANDIDATE GENES FOR TRANSACTIVATION BY P53

The p53 protein is known to trans-activate a number of genes by specif ic binding to a consensus sequence containing two decamers of the type : PuPuPuCA/TT/AGPyPyPy. In order to identify new p53 trans-activated g enes, we defined a set of criteria for computer search of p53-responsi ve elements, Based on experimental data, we proposed an extended conse nsus sequence composed of the two decamers of the El-Deiry consensus s equence flanked by two additional ones, A maximum of 3 bp substitution s 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 iden tifying within the promoter region of the IGF-BP3 gene the existence o f a novel p53-responsive element whose functional significance was ver ified, 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 sequ ences were first analysed, Among the oncogenes, kinases, proteases and structural proteins, 55 new genes were selected; six of them were ret rieved in more than one species