p53—Guardian Angel and Archangel

ABSTRACT

p53 is a master regulator of the cell cycle, capable of assessing the severity and the scope of damage to the cellular DNA, integrating the signals from the cell under stress and delivering the final decision about the destiny of the cell—undertaking repair activities; entering replicative senescence; inducing cell death; resorting to translesion transactions or altering the metabolism or the expression pattern of the cell. Proper functioning of p53 and its related pathways is essential in multicellular eukaryotes, with failures in the DNA-binding and transactivation properties of p53 usually resulting in cancer. Recent research on some common polymorphic variants of p53 that exhibit differential properties in their ability to induce cell cycle arrest or apoptosis indicate that p53 is not only the ‘guardian angel’ of the genome, as is commonly believed, keeping its integrity in check and disposing of damaged cells, but it is as well the ‘archangel’ that is responsible for cutting down the lifespan of the organism by the mechanism of ageing. One function can hardly exist without the other, and it is very individual as to whether carriership of one polymorphic form or another would be beneficial in the particular case, considering the general status of the patient and the specificities of the pathogenesis of the disease or condition in question. Age of the patient seems to be a major determining factor, as the differential pattern in the properties of p53 seems to become more pronounced as age advances.

Keywords:

• p53
• DNA repair
• apoptosis
• genetic polymorphism
• cancer
• longevity