Most mutant p53 heterozygous tumours undergo loss of the remaining wildtype (WT) p53 allele which leads to stabilization of the mutant p53 protein. Here, the authors show in an autochthonous colorectal cancer model that the WT p53 allele retains partial activity and suppresses the heat shock factor 1 (HSF1)- chaperone axis to prevent mutant p53 stabilisation and mutant p53 gain-of-function activities, thereby creating selective pressure for p53 loss-of-heterozygosity.
- Tamara Isermann
- Özge Çiçek Şener
- Ramona Schulz-Heddergott