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Protein Palmitoylation in Cancer

  • Sonia LoboEmail author
Chapter

Abstract

Protein palmitoylation describes the posttranslational addition of the 16-carbon fatty acid, palmitate, to specific cysteine of proteins via a labile thioester bond. Unlike other forms of lipidation, such as myristoylation and prenylation, palmitoylation is reversible, allowing for dynamic regulation of protein-membrane interactions, protein trafficking between membrane compartments, protein-protein interactions, and protein function. Recent proteomic studies have revealed that the number of palmitoylated proteins in mammals is both abundant and diverse; curation of data from such studies has demonstrated that genes encoding palmitoylated proteins constitute 10% of the genome and that palmitoylation is enriched equally in cancer, at neuronal synapses, and in disorders of the nervous system. This suggests that a disruption in the homeostatic balance of protein palmitoylation can have critical pathophysiological consequences. Palmitoyl acyltransferases (PATs) catalyze the transfer of palmitate to a substrate, while depalmitoylation is mediated by acyl-protein thioesterases (APTs). To date, nearly half of the 23 genes that encode PATs and several APT genes have been linked to tumorigenesis, representing important targets for cancer drug development. While convincing evidence for a role for aberrant palmitoylation in cancer remains to be established, the number of cancer-related signaling proteins and networks in which palmitoylation plays a pivotal role is large and growing. Developing pharmacological modulators of palmitoylation to prevent or reverse cancer progression will require that they be developed within the context of well-characterized PAT-/APT-related signaling systems implicated in cancer.

Keywords

Palmitoylation Palmitoyl acyltransferases Acyl-protein thioesterases Posttranslational modification Cancer 

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Geisinger Commonwealth School of MedicineScrantonUSA

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