Discovery of protein-palmitoylating enzymes
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Posttranslational modification provides proteins with additional function and regulatory control beyond genomic information, allowing cells to maintain homeostasis and respond to extracellular signals. Protein palmitoylation, the common posttranslational modification with the lipid palmitate, plays a pivotal role in protein trafficking and function. Palmitoylation is unique in that it is reversible and dynamically regulated by specific extracellular signals. The reversible nature of protein palmitoylation enables proteins to shuttle between intracellular compartments upon extracellular signals. However, the molecular mechanisms of protein palmitoylation have long been elusive, mostly because the enzymes responsible for protein palmitoylation were unknown. Recently, genetically conserved DHHC family proteins have emerged as palmitoyl-acyl transferases. With the identification of specific enzymes for palmitoylated proteins, including H-Ras, PSD-95, and eNOS, the specificity and regulatory mechanism of DHHC enzymes are beginning to be clarified.
KeywordsProtein palmitoylation DHHC protein Lipid modification Protein targeting Palmitoyl-acyl transferase
We thank Dr. Catherine H. Berlot of the Weis Center for Research for kind gifts of Gαq-GFP plasmids, Dr. David S. Bredt of Eli Lilly and company for helpful suggestions and Dr. Jun Noritake for reading the manuscript. R.T. is supported by the Japan Society for the Promotion of Science. Y.F. is supported by the Human Frontier Science Program (HFSP) and Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (grant no. 18700376). M.F. is supported by grants from the HFSP, MEXT (nos. 18022054, 18057032, and 18687008) and the Ministry of Health, Labour and Welfare of Japan (no. 17C-2).
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