Profiling of protein depalmitoylation during adipogenesis using activity-based probes

Modulation of adipogenesis is one of the most promising targets in the search for therapies against obesity. Given the large lipid pool present in adipocytes, it is likely that protein (de)palmitoylation plays a role during their differentiation. However, this post-translational modification is understudied in this process. In an in vitro model of adipogenesis, I therefore aim to (1) identify the substrates that are (de)palmitoylated, (2) profile protein depalmitoylases using chemical probes , and (3) shed light on the activity and cellular localization of two protein depalmitoylases, namely APT1 and APT2. To this end, I will identify targets for (de)palmitoylation using a chemical proteomics workflow on OP9 cells differentiating to adipocytes and develop several types of chemical probes to study APT1 and APT2. I will apply these tools in fluorescence microscopy and proteomics experiments to measure the activity and localization of APT1 and APT2 during adipogenesis.