NEW STRATEGY TURNS ON ACETYLATION OF PROTEINS

摘要

Acetylation is one of the most common protein modifications in eukaryotes. One such reaction, known as lysine acetylation, occurs when an acetyl group is attached to lysine, an amino acid used to build proteins in our bodies. This, in turn, impacts protein function, protein stability, and protein-protein interaction in cells, all of which are especially relevant for many common diseases such as obesity, diabetes mellitus, neurodegenerative disorders, and cancer. However, investigating protein acetylation is tricky-the methods are usually nonspecific and lack control of timing and magnitude. In a new study, Christopher G. Parker and co-workers have created a genetically encoded acetylation tagging platform, AceTAG, to drive the acetylation of proteins (DOI:10.1021/ jacs.1c07850). By using heterobifunctional molecules, they have successfully targeted selective acetylation of functionally relevant sites on p53, H3.3, and p6S/RelA in cells and showed that their reaction is dose-controlled, reversible, and selective and occurs within minutes for tagged proteins. For the team, the next few steps are to probe AceTAG as a tool to explore endogenous proteins for acetylation, as well as a therapeutic strategy.