Chemical approaches for profiling dynamic palmitoylation

Protein palmitoylation is a critical post-translational modification important for membrane compartmentalization, trafficking and regulation of many key signalling proteins. Recent non-radioactive chemo-proteomic labelling methods have enabled a new focus on this emerging regulatory modification. Palmitoylated proteins can now be profiled in complex biological systems by MS for direct annotation and quantification. Based on these analyses, palmitoylation is clearly widespread and broadly influences the function of many cellular pathways. The recent introduction of selective chemical labelling approaches has opened new opportunities to revisit long-held questions about the enzymatic regulation of this widespread post-translational modification. In the present review, we discuss the impact of new chemical labelling approaches and future challenges for the dynamic global analysis of protein palmitoylation.