Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

During the last 23 years, investigation of the p53 gene and its respective protein product became a major focus in cancer research. It has been established that the p53 protein plays an important role in preventing tumour development and that a majority of cancers show evidence of loss of the p53 function (Hollstein et al., 1994). Alterations of the p53 tumour suppressor gene and its encoded protein are the most frequently encountered genetic events in human malignancies (Hollstein et al., 1991). More than a half of the human tumours contain somatic mutations in p53 that inactivate its function. Furthermore, germline mutations in p53 are responsible for the majority of cases of the inherited cancer family syndrome known as Li-Fraumeni syndrome (Malkin et al., 1990). The p53 is a well-known tumour suppressor affecting - through regulation of expression of different target genes - important cellular processes like cell cycle progression, apoptosis and senescence. These activities were linked to the ability of the p53 protein to act as a powerful transcription factor that binds to as many as 300 different promoter elements in the genome, thus profoundly altering patterns of specific gene expression (Zhao et al., 2000; Lane and Lain, 2002). The transcriptional activity of the p53 protein is activated in response to cellular stress such as DNA damage or oncogene activation and is very highly regulated. All attempts to find p53-related genes had been unsuccessful until 1997. The realization that p53 in fact belongs to a family of related genes came almost 20 years after the discovery of p53 (Yang and McKeon, 2000) when in 1997 Kaghad et al. (Kaghad et al., 1997) discovered cDNA encoding the p73 protein in the hybridization screen of a COS-cell cDNA library using degenerative oligonucleotide primers for different genes. During subsequent screening they found existence of cDNAs encoding p73α and p73β, which are splice variants of p53 differing at their C-termini. The TP73 gene maps to the 1p36.2-3 chromosome region (tumour suppressor gene locus the existence of which was suspected for a long time), in which deletions frequently appear in neuroblastoma, colon cancer, melanoma and breast cancer (Schwab et al., 1996). Based on all new findings it has been hypothesized that p73 could be a new tumour suppressor protein. In 1998, another p53 homologue - p63 protein (Yang et al., 1998) was described, which maps to the 3q27-29 chromosome region. These facts stimulated further p73 and p63 protein studies, whose number is rising exponentially.

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