Protein S-palmitoylation and cancer

• S-palmitoylation regulates protein location, trafficking and function.
• Dysregulation of protein S-palmitoylation contributes to human cancer.
• Abnormalities in a large number of DHHC palmitoyltransferases are found in cancers.
• Palmitoyltransferases and depalmitoylases are potential targets for cancer therapy.

Protein S-palmitoylation is a reversible posttranslational modification of proteins with fatty acids, an enzymatic process driven by a recently discovered family of protein acyltransferases (PATs) that are defined by a conserved catalytic domain characterized by a DHHC sequence motif. Protein S-palmitoylation has a prominent role in regulating protein location, trafficking and function. Recent studies of DHHC PATs and their functional effects have demonstrated that their dysregulation is associated with human diseases, including schizophrenia, X-linked mental retardation, and Huntington's Disease. A growing number of reports indicate an important role for DHHC proteins and their substrates in tumorigenesis. Whereas DHHC PATs comprise a family of 23 enzymes in humans, a smaller number of enzymes that remove palmitate have been identified and characterized as potential therapeutic targets. Here we review current knowledge of the enzymes that mediate reversible palmitoylation and their cancer-associated substrates and discuss potential therapeutic applications.