Mutant p53 – Heat Shock Response Oncogenic Cooperation: A New Mechanism of Cancer Cell Survival

摘要: The main tumor suppressor function of p53 as a ‘guardian the genome’ is to respond cellular stress by transcriptional activation apoptosis, growth arrest or senescence in damaged cells. Not surprisingly, mutations gene are most frequent genetic alteration human cancers. Importantly, mutant (mutp53) proteins not only lose their wild-type activity, but also can actively promote development. Two mechanisms accounting for mutp53 proto-oncogenic activity inhibition dominant-negative fashion and gain additional oncogenic activities known gain-of-function (GOF). Here we discuss novel mechanism GOF, which relies on its cooperation with heat shock machinery. This coordinated adaptive renders cancer cells more resistant proteotoxic provides both, strong survival advantage promising means therapeutic intervention.