In many disease states, it would be beneficial to be able to inhibit the heat shock response and heat shock proteins (Hsps). For example, in cancer, Hsps are expressed at high levels and help to create a fostering environment for tumor cell growth and tumor development. Hsp90 is a specialized ATP-dependent molecular chaperone required for the stability and function of hundreds of so called client proteins, many of which are signalling proteins involved in oncogenesis and growth-related signalling events. Therefore, Hsp90 is an attractive target for anticancer therapies. We are working with both natural products and synthetic compounds in the lab that may target different Hsps. Our goal is to use these compounds as tools to learn more about the heat shock response and HSFs, and how they can be modulated.
The research is done in the laboratory of Pia Roos-Mattjus.
Gambogic acid and gambogenic acid induce a thiol-dependent heat shock response and disrupt the interaction between HSP90 and HSF1 or HSF2.
Pesonen L, Svartsjö S, Bäck V, de Thonel A, Mezger V, Sabéran-Djoneidi D, Roos-Mattjus P.
Cell Stress Chaperones 2021 Sep;26(5):819-833. doi: 10.1007/s12192-021-01222-4.