Signalling pathways controlling protein degradation upon stress

Increasing evidence shows that alterations and mutations in the UPS give rise to various human diseases, such as cancer and neurodegenerative disorders. Our interest is to understand how the activity of the ubiquitin-proteasome system is regulated in cells so that accumulation of unfolded, misfolded, or damaged proteins can be cleared before they become deleterious. We recently reported that proteasomal degradation is regulated upon proteotoxic stresses in a phosphorylation-dependent manner (Rousseau and Bertolotti, 2016, Nature). The new project will focus on how protein phosphorylation events regulate protein homeostasis and cell survival. An additional project consists in developing new tools to characterize how proteasome homeostasis is regulated in cells, and to use these tools to identify new regulators and drugs modulating proteasomal degradation. Both yeast and mammalian systems will be used for this project.