Understanding the principles of protein homeostasis in cancer and aging
The maintenance of protein homeostasis, or proteostasis, involves folding and degradation of damaged proteins. It is commonly thought that age-related impairment of protein quality control (PQC) affects general proteostasis networks, causing enhanced aggregation of misfolded proteins that can be toxic for cells and shortens organismal lifespan.The ubiquitin/proteasome system (UPS) is a major proteolytic route functioning in a cellular network that maintains the proteome during stress and aging. Another proteolytic system supporting proteostasis is the autophagy-lysosome pathway that degrades proteins inside activated autophagosomes. Defective functionality of either of these systems causes enhanced protein aggregation and affects lifespan, suggesting mechanistic overlap and cooperation between UPS and autophagy in stress and aging. The ultimate goal of our research is to assemble a global picture of stress-induced proteolytic networks critical for health of multicellular organisms.