n²STAR Seminar by Prof. Volker Dötsch

Inactivation of the tumor suppressor p53, also known as the guardian of the genome, is one of the most common hallmarks of human cancer. In more than 50 % of all tumors, this inactivation is caused by mutations that are mainly located at several hotspots within the DNA binding domain. Some of the hotspot mutations do not only lead to the inactivation of p53 but also its destabilization causing conformational changes of the DBD or even unfolding and the exposure of aggregation-prone regions. Those mutants are described as temperature-sensitive mutants as they adopt a wild-type conformation at lower temperatures but get destabilized at elevated temperatures.