Complementation of two mutant p53: implications for loss of heterozygosity in cancer

Remarkably, a cancer cell rarely possesses two mutant p53 proteins. Instead, mutation of one allele is usually associated with loss of the second p53 allele. Why do not two mutant p53 co-exist? We hypothesize that two different p53 may complement each other, when expressed at equal levels. By titrating trans-deficient and DNA-binding-deficient p53 in cells with mutant p53 and by co-transfecting distinct mutant p53 in p53-null cells, we demonstrated activation of p53-dependent transcription. We suggest that, due to complementation of two mutant p53, cancer cells need to delete the second p53 allele rather than mutate it.