S-acylation by the DHHC protein family

2010 ◽  
Vol 38 (2) ◽  
pp. 522-524 ◽  
Author(s):  
Jennifer Greaves ◽  
Luke H. Chamberlain
Keyword(s):  
Substrate Specificity ◽  
Protein S ◽  
Protein Family ◽  
Target Proteins ◽  
Dhhc Protein

A family of 23 DHHC (Asp-His-His-Cys) proteins that function as mammalian S-acyltransferases has been identified, reinvigorating the study of protein S-acylation. Recent studies have continued to reveal how S-acylation affects target proteins, and have provided glimpses of how DHHC-substrate specificity might be achieved.

scholarly journals DHHC protein family targets different subsets of glioma stem cells in specific niches

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Xueran Chen ◽  
Lei Hu ◽  
Haoran Yang ◽  
Huihui Ma ◽  
Kaiqin Ye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Family ◽  
Glioma Stem Cells ◽  
Dhhc Protein

scholarly journals Therapeutic targeting of protein S-acylation for the treatment of disease

2019 ◽  
Vol 48 (1) ◽  
pp. 281-290 ◽  
Author(s):  
Niall J. Fraser ◽  
Jacqueline Howie ◽  
Krzysztof J. Wypijewski ◽  
William Fuller
Keyword(s):  
Critical Role ◽  
Cardiac Contractility ◽  
Protein S ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Specific Target ◽  
Receptor Signalling ◽  
Therapeutic Drugs ◽  
Wide Range

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.

scholarly journals Development of an Acrylamide-Based Inhibitor of Protein S-Acylation

2021 ◽  
Author(s):  
Saara-Anne Azizi ◽  
Tong Lan ◽  
Clémence Delalande ◽  
Rahul Kathayat ◽  
Bryan Dickinson
Keyword(s):  
Cell Signaling ◽  
Human Disease ◽  
Cellular Signaling ◽  
Protein S ◽  
Live Cells ◽  
Synthesis And Characterization ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Cellular Events

<div><div><div><p>Protein S-acylation is a dynamic lipid post-translational modification that can modulate the localization and activity of target proteins. In humans, the installation of the lipid onto target proteins is catalyzed by a family of 23 Asp-His-His-Cys domain-containing protein acyltransferases (DHHC-PATs). DHHCs are increasingly recognized as critical players in cellular signaling events and in human disease. However, progress elucidating the functions and mechanisms of DHHC “writers” has been hampered by a lack of chemical tools to perturb their activity in live cells. Herein, we report the synthesis and characterization of PATi, a pan- DHHC inhibitor more potent than 2-bromopalmitate (2BP), the most commonly used DHHC inhibitor in the field. Possessing an acrylamide warhead, PATi pairs its gain in potency with decreases in both toxicity and inhibition of the S-acylation eraser enzymes – two of the major weaknesses of 2BP. Our studies show that PATi engages with DHHC family proteins in cells, inhibits protein S-acylation, and disrupts DHHC-regulated cellular events. PATi represents an improved chemical tool for untangling the complexities of DHHC-mediated cell signaling by protein S-acylation.</p></div></div></div>

scholarly journals Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family

2018 ◽  
Vol 5 (6) ◽  
pp. 280-292 ◽  
Author(s):  
Anezia Kourkoulou ◽  
Alexandros A. Pittis ◽  
George Diallinas
Keyword(s):  
Substrate Specificity ◽  
Protein Family

scholarly journals Role of hydrogen sulfide and polysulfides in neurological diseases: focus on protein S-Persulfidation

2020 ◽  
Vol 18 ◽  
Author(s):  
Hai-Jian Sun ◽  
Zhi-Yuan Wu ◽  
Xiao-Wei Nie ◽  
Jin-Song Bian
Keyword(s):  
Hydrogen Sulfide ◽  
Protein Modification ◽  
Neurological Diseases ◽  
Protein S ◽  
The Body ◽  
Memory Decline ◽  
Target Proteins ◽  
Therapeutic Development ◽  
The Central Nervous System

: Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post-translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins.

scholarly journals The Role of Protein S-Nitrosylation in Protein Misfolding-Associated Diseases

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 705
Author(s):  
Yun-Jin Ju ◽  
Hye-Won Lee ◽  
Ji-Woong Choi ◽  
Min-Sik Choi
Keyword(s):  
Protein Misfolding ◽  
Nitrosative Stress ◽  
Protein S ◽  
Misfolded Proteins ◽  
No Production ◽  
Target Proteins ◽  
Ubiquitin Protein Ligase ◽  
Associated Diseases ◽  
The Relationship

Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.

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