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Regulatory effects of post-translational modifications on zDHHC S-acyltransferases

The human zDHHC S-acyltransferase family comprises 23 enzymes that mediate the S-acylation of a multitude of cellular proteins, including channels, receptors, transporters, signaling molecules, scaffolds, and chaperones. This reversible post-transitional modification (PTM) involves the attachment of...

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Autores principales: Zmuda, Filip, Chamberlain, Luke H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586229/
https://www.ncbi.nlm.nih.gov/pubmed/32817054
http://dx.doi.org/10.1074/jbc.REV120.014717
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author Zmuda, Filip
Chamberlain, Luke H.
author_facet Zmuda, Filip
Chamberlain, Luke H.
author_sort Zmuda, Filip
collection PubMed
description The human zDHHC S-acyltransferase family comprises 23 enzymes that mediate the S-acylation of a multitude of cellular proteins, including channels, receptors, transporters, signaling molecules, scaffolds, and chaperones. This reversible post-transitional modification (PTM) involves the attachment of a fatty acyl chain, usually derived from palmitoyl-CoA, to specific cysteine residues on target proteins, which affects their stability, localization, and function. These outcomes are essential to control many processes, including synaptic transmission and plasticity, cell growth and differentiation, and infectivity of viruses and other pathogens. Given the physiological importance of S-acylation, it is unsurprising that perturbations in this process, including mutations in ZDHHC genes, have been linked to different neurological pathologies and cancers, and there is growing interest in zDHHC enzymes as novel drug targets. Although zDHHC enzymes control a diverse array of cellular processes and are associated with major disorders, our understanding of these enzymes is surprisingly incomplete, particularly with regard to the regulatory mechanisms controlling these enzymes. However, there is growing evidence highlighting the role of different PTMs in this process. In this review, we discuss how PTMs, including phosphorylation, S-acylation, and ubiquitination, affect the stability, localization, and function of zDHHC enzymes and speculate on possible effects of PTMs that have emerged from larger screening studies. Developing a better understanding of the regulatory effects of PTMs on zDHHC enzymes will provide new insight into the intracellular dynamics of S-acylation and may also highlight novel approaches to modulate S-acylation for clinical gain.
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spelling pubmed-75862292020-10-28 Regulatory effects of post-translational modifications on zDHHC S-acyltransferases Zmuda, Filip Chamberlain, Luke H. J Biol Chem JBC Reviews The human zDHHC S-acyltransferase family comprises 23 enzymes that mediate the S-acylation of a multitude of cellular proteins, including channels, receptors, transporters, signaling molecules, scaffolds, and chaperones. This reversible post-transitional modification (PTM) involves the attachment of a fatty acyl chain, usually derived from palmitoyl-CoA, to specific cysteine residues on target proteins, which affects their stability, localization, and function. These outcomes are essential to control many processes, including synaptic transmission and plasticity, cell growth and differentiation, and infectivity of viruses and other pathogens. Given the physiological importance of S-acylation, it is unsurprising that perturbations in this process, including mutations in ZDHHC genes, have been linked to different neurological pathologies and cancers, and there is growing interest in zDHHC enzymes as novel drug targets. Although zDHHC enzymes control a diverse array of cellular processes and are associated with major disorders, our understanding of these enzymes is surprisingly incomplete, particularly with regard to the regulatory mechanisms controlling these enzymes. However, there is growing evidence highlighting the role of different PTMs in this process. In this review, we discuss how PTMs, including phosphorylation, S-acylation, and ubiquitination, affect the stability, localization, and function of zDHHC enzymes and speculate on possible effects of PTMs that have emerged from larger screening studies. Developing a better understanding of the regulatory effects of PTMs on zDHHC enzymes will provide new insight into the intracellular dynamics of S-acylation and may also highlight novel approaches to modulate S-acylation for clinical gain. American Society for Biochemistry and Molecular Biology 2020-10-23 2020-08-17 /pmc/articles/PMC7586229/ /pubmed/32817054 http://dx.doi.org/10.1074/jbc.REV120.014717 Text en © 2020 Zmuda and Chamberlain. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle JBC Reviews
Zmuda, Filip
Chamberlain, Luke H.
Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title_full Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title_fullStr Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title_full_unstemmed Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title_short Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
title_sort regulatory effects of post-translational modifications on zdhhc s-acyltransferases
topic JBC Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586229/
https://www.ncbi.nlm.nih.gov/pubmed/32817054
http://dx.doi.org/10.1074/jbc.REV120.014717
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