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).
KeywordsNeuronal Cell Death Kainic Acid Mouse Double Minute Free Ubiquitin Intractable Temporal Lobe Epilepsy
- Brooks CL, Gu W (2004) Dynamics in the p53-Mdm2 ubiquitination pathway. Cell Cycle 3:895–899Google Scholar
- Deb SP (2002) Function and dysfunction of the human oncoprotein MDM2. Front Biosci 7:d235–d243Google Scholar
- Efeyan A, Serrano M (2007) p53: Guardian of the genome and policeman of the oncogenes. Cell Cycle 6:1006–1010Google Scholar
- Hughes PE, Alexi T, Schreiber SS (1997) Minireview: A role for the tumour-suppressor gene p53 in neuronal apoptosis. NeuroReport 8:v–xiGoogle Scholar
- Iwakuma T, Lozano G, Flores ER (2005) Li-Fraumeni syndrome: A p53 family affair. Cell Cycle 4:865–867Google Scholar
- Meek DW (1997) Post-translational modification of p53 and the integration of stress signals. Pathol Biol (Paris) 45:804–814Google Scholar