Individual Variation in p53 Responsiveness Mats Ljungman

The tumor suppressor p53 is part of the cellular emergency team that is designated to respond to various cellular stresses such as DNA damage. After exposure to UV or ionizing radia-tion, p53 proteins accumulate in the nucleus and transactivate specific target genes. Expression of the p53-inducible p21WAF1 gene product enhances the survival of cells by activating cell cycle checkpoints, thus allowing the cell to have more time for DNA repair before entering S phase or mitosis. However, p53 can also stimulate cells to undergo apoptosis, a programmed cell death pathway. These activities of p53 contribute to the protec-tion of the organism from acquiring mutated cells and thus sup-press tumor formation (1). Although UV and ionizing radiation are both physical DNA-damaging agents that induce p53, the types of lesions induced in DNA are quite different, as are the signal transduction pathway