Tumor Suppressor P53: A Multifunctional Protein Implicated In Seizure-Induced Neuronal Cell Death

It is ironic that the p53 “tumor antigen”, first discovered more than 20 years ago, was initially thought to play a major role in promoting tumorigenesis (Parada et al. 1984). It was not long after, however, that the p53 protein was found to be a potent tumor suppressor. In fact, since the mid1990s, p53 has been regarded as the “guardian of the genome” on the basis of its ability to block the proliferation of cells with mutated DNA (Lane 1992). For more than two decades, tumor suppressor p53 has been among the most widely studied proteins. Notably, the myriad cellular functions in which p53 is involved continue to increase (Levine et al. 2006; Efeyan and Serrano 2007; Fuster et al. 2007). The human p53 protein consists of 393 amino acid residues and has a molecular weight of approximately 53 kDa. The p53 gene product is a modular molecule that consists of three well-characterized functional domains: an N-terminal transactivation domain (residues 1–42), a central sequence-specific DNA binding domain (residues 102–292), and a highly basic C-terminal domain that regulates p53 oligomerization and sequence-specific DNA binding (Fig. 15.1) (Prives and Hall 1999; Lavin and Gueven 2006).