Protein palmitoylation and its pathophysiological relevance

Protein palmitoylation, in which C16 fatty acid chains are attached to cysteine residues via a reversible thioester linkage, is one of the most common lipid modifications and plays important roles in regulating protein stability, subcellular localization, membrane trafficking, interactions with effector proteins, enzymatic activity, and a variety of other cellular processes. Moreover, the unique reversibility of palmitoylation allows proteins to be rapidly shuttled between biological membranes and cytoplasmic substrates in a process usually controlled by a member of the DHHC family of protein palmitoyl transferases (PATs). Notably, mutations in PATs are closely related to a variety of human diseases, such as cancer, neurological disorders, and immune deficiency conditions. In addition to PATs, intracellular palmitoylation dynamics are also regulated by the interplay between distinct posttranslational modifications, including ubiquitination and phosphorylation. Understanding the specific mechanisms of palmitoylation may reveal novel potential therapeutic targets for many human diseases. Protein can be palmitoylated in golgi apparatus by the DHHC‐family, which add a molecule of palmitic acid to the protein. The palmitoylated proteins would traffic to PM via either vesicular transport or diffusion, and then generally translocate to lipid rafts; depalmitoylation is catalyzed by either APT in cytoplasm or PPT1/2 in lysosome, and the depalmitoylated protein would diffuses back to the Golgi complex where it can be palmitoylated for another cycle.