Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

The p53 tumour suppressor gene is the most frequent target for genetic alterations in human tumours (Nigro et al., 1989; Hollstein et al., 1991) and encodes a nuclear phosphoprotein which plays a key role in cell cycle regulation. This protein protects cells from undergoing tumorigenic alterations by inducing either cell cycle arrest or programmed cell death in response to a variety of cellular stress signals (Ko and Prives, 1996; Levine, 1997) and also plays an important role in maintaining the integrity of the genome (Lane, 1992). Attempts to find p53 homologues analogous to the pRb family of tumour suppressors were successful and a new gene, p73, has been identified on the short arm of chromosome 1 in a region frequently deleted in neuroblastoma (Kaghad et al., 1997; Yang et al., 1998). This gene encodes several proteins with structural and functional homology to p53 (De Laurenzi et al., 1998) that can activate transcription of the p21^WAF1 gene responsible for cell-cycle arrest, and can also induce apoptosis when overexpressed (Jost et al., 1997; Kaghad et al., 1997). There are several differentially spliced variants of mRNAs, which are translated into different p73 proteins. This splicing occurs at the 3' end of the sequence and translated proteins have differing C-termini, in which p73α is a full-length protein and the β and δ isoforms are truncated forms of this protein. The δ isoform lacking the major part of the C-terminal region is most similar to p53. The γ isoform contains a different 75-residue C-terminus compared to the α isoform due to a long alternative reading frame in this region (Kaghad et al., 1997; De Laurenzi et al., 1998; De Laurenzi et al., 1999; Ueda et al., 1999). p73 as well as p53 contains a transactivation domain, a DNA-binding domain and an oligomerization domain. The highest level of homology is exhibited in the DNA-binding domain (63% identity between the p53 and p73), and this finding suggests that both these proteins can bind to the same DNA sequences and transactivate the same target genes. The conservation of high homology in the oligomerization domain suggests that the members of this family could form mixed oligomers. Although the existence of these mixed oligomers in vivo is still open to question, the availability of specific antibodies could help to address this problem. The identification of a family of p53-related transcription factors that can be potentially redundant in their ability to activate the same cellular responses (i.e. cell-cycle arrest and apoptosis) has encouraged a study into the basis for their similarities and differences in terms of their physical and functional interactions with one another, their mechanism of activation and their regulation. Monoclonal antibodies specific to different forms of the p73 protein therefore provide a powerful tool to study these proteins both in vivo and in vitro.

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