Figure 1.

Acquisition and impact of mutant p53 status. Expression of a mutant p53 protein is associated with more aggressive behavior in many cancer types, and mutant p53 status may be acquired through several mechanisms. Following point mutation in TP53, cancer cells can become genetically homozygous or hemizygous through loss of the WT allele (loss of heterozygosity). However, in cells that retain WT p53, the dominant-negative activity of mutant p53 can inhibit the WT protein and render the cell functionally mutant for p53. Finally, the adoption of a pseudomutant p53 conformation by the WT protein can allow mutant p53 behavior in cells without a TP53 mutation. Additional gain-of-function activities of mutant p53, beyond loss of WT activities, are associated with progression to metastasis in several cancer types.