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. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.Ni. All rights reserved.