Supervisor Project : Role of protein Ubiquitylation in the Proteasome-Autophagy Crosstalk
Multiple aspects regarding the biological relevance of distinct Ub chains and their role in the connection of between the Proteasome and Autophagy pathways remain unexplored. To address these questions our group has developed molecular traps (Tandem Ub Binding Entities or TUBEs) to capture and identify proteins modified by members of the Ub family. Here we propose the use of new molecular traps based in UBD from proteins implicated in autophagy (e.g. p62): i) Ubiquitylated proteins will be identified using a TUBEs-MS approach; ii) To study their specificity, captured proteins will be compared to those proteins captured with distinct Ub traps; iii) Ubiquitylated proteins-UDB interactions will also be studied using small inhibitor molecules; iv) Role of identified factors in UPS-Autophagy crosstalk under proteotoxic stress conditions will be analysed.