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

Filip Zmuda, Luke H. Chamberlain

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
29 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)14640-14652
Number of pages13
JournalJournal of Biological Chemistry
Issue number43
Early online date17 Aug 2020
Publication statusPublished - 23 Oct 2020


  • protein acylation
  • post-translational modification (PTM)
  • protein palmitoylation
  • protein chemical modification
  • S-acylation
  • zDHHC enzyme
  • phosphorylation
  • ubiquitination
  • acetylation
  • methylation


Dive into the research topics of 'Regulatory effects of post-translational modifications on zDHHC S-acyltransferases'. Together they form a unique fingerprint.

Cite this