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Therapeutic targeting of protein S-acylation for the treatment of disease.
- Source :
-
Biochemical Society transactions [Biochem Soc Trans] 2020 Feb 28; Vol. 48 (1), pp. 281-290. - Publication Year :
- 2020
-
Abstract
- The post-translational modification protein S-acylation (commonly known as palmitoylation) plays a critical role in regulating a wide range of biological processes including cell growth, cardiac contractility, synaptic plasticity, endocytosis, vesicle trafficking, membrane transport and biased-receptor signalling. As a consequence, zDHHC-protein acyl transferases (zDHHC-PATs), enzymes that catalyse the addition of fatty acid groups to specific cysteine residues on target proteins, and acyl proteins thioesterases, proteins that hydrolyse thioester linkages, are important pharmaceutical targets. At present, no therapeutic drugs have been developed that act by changing the palmitoylation status of specific target proteins. Here, we consider the role that palmitoylation plays in the development of diseases such as cancer and detail possible strategies for selectively manipulating the palmitoylation status of specific target proteins, a necessary first step towards developing clinically useful molecules for the treatment of disease.<br /> (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Subjects :
- Animals
Cysteine metabolism
Drug Discovery methods
Humans
Lipoylation physiology
Mice
Neoplasms metabolism
Palmitoyl-CoA Hydrolase metabolism
Protein Processing, Post-Translational
Acyltransferases metabolism
B7-H1 Antigen metabolism
Lipoylation drug effects
Neoplasms drug therapy
Receptor, Melanocortin, Type 1 metabolism
ras Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8752
- Volume :
- 48
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical Society transactions
- Publication Type :
- Academic Journal
- Accession number :
- 31872231
- Full Text :
- https://doi.org/10.1042/BST20190707