title: Palmitoyl acyltransferases, their substrates, and novel assays to connect them (Review).
abstract: Thio-palmitoylation is the post-translational addition of the 16-carbon fatty acid, palmitate, to the thiol side chain of cysteine residues by a labile thioester bond. Palmitoylation increases the lipophilicity of a protein resulting in dramatic changes in its subcellular distribution such as moving from the endoplasmic reticulum to the plasma membrane or in subtle changes like an increased affinity for cholesterol-rich lipid rafts in membranes. Palmitoylation is also dynamic, making it unique among post-translational protein lipid modifications. Discovering the molecular identity of palmitoyl acyltransferases (PATs) was a watershed event that dramatically accelerated the pace of discovery in the field. Likewise, there has been increased interest in palmitoylation partly because many of the genes encoding PATs have been linked to cancer and other diseases. Now, with a greater understanding of how palmitate is enzymatically attached to proteins, some of the most interesting questions include: What are the substrates of each PAT?; how does a PAT recognize and palmitoylate a substrate?; how are PATs regulated?; and, how is depalmitoylation regulated? The answers to these questions are beginning to unfold due to the recent development of novel assays as well as the expansion and refinement of existing assays. Our ability to understand palmitoylation and its importance to human health and disease is only as good as the methods we use to test our hypotheses. The continued development of methods with increased sensitivity and selectivity is critical to this venture.
authors.affiliation: The Commonwealth Medical College, Scranton, Pennsylvania, USA.
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Planey
authors.forename: David A
authors.initials: DA
authors.lastname: Zacharias
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D054878:Lipoylation; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
chemical_list: D000217:Acyltransferases