Role of S-palmitoylation in digestive system diseases

Abstract Digestive system diseases, including liver diseases, gastrointestinal cancers, and inflammatory bowel diseases, pose major health challenges worldwide. These conditions are influenced by a range of key metabolic signaling pathways, many of which are regulated by palmitoylation. Palmitoylati...

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Main Authors: Hanqing Li, Qiuxiang Yuan, Shuangshuang Wang, Tao Yu, Xingsi Qi
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02629-z
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author Hanqing Li
Qiuxiang Yuan
Shuangshuang Wang
Tao Yu
Xingsi Qi
author_facet Hanqing Li
Qiuxiang Yuan
Shuangshuang Wang
Tao Yu
Xingsi Qi
author_sort Hanqing Li
collection DOAJ
description Abstract Digestive system diseases, including liver diseases, gastrointestinal cancers, and inflammatory bowel diseases, pose major health challenges worldwide. These conditions are influenced by a range of key metabolic signaling pathways, many of which are regulated by palmitoylation. Palmitoylation is a type of lipid modification catalyzed by DHHC palmitoyl S-acyltransferases (DHHC-PTAs) and depalmitoylases, which play critical roles in modulating protein localization, stability, and signal transduction. Dysregulation of S-palmitoylation is closely associated with numerous diseases, including these of the digestive system, through multiple key processes such as immune responses, lipid metabolism, and cellular signaling. Decades of investigations have driven the development of a large body of inhibitors targeting zDHHCs and depalmitoylases, such as S-(2-acetamidoethyl) 2-bromohexadecanethioate (MY-D-4), Artemisinin and Lomitapide. This review provides a comprehensive summary of the role of palmitoylation in digestive system diseases, discusses its effect on disease mechanisms. By elucidating the regulatory functions of palmitoylation under these conditions, this review aimed to identify new strategies for the diagnosis and treatment of digestive system disorders.
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spelling doaj-art-2db7b78010b74d3bb277f2c5a0e75c2e2025-08-20T04:01:46ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111810.1038/s41420-025-02629-zRole of S-palmitoylation in digestive system diseasesHanqing Li0Qiuxiang Yuan1Shuangshuang Wang2Tao Yu3Xingsi Qi4Department of Gastroenterology, The People’s Hospital of Qingdao ChengyangDepartment of Gastroenterology, The People’s Hospital of Qingdao ChengyangDepartment of Gastroenterology, The People’s Hospital of Qingdao ChengyangInstitute for Translational Medicine, The Affiliated Hospital of Qingdao UniversityDepartment of Gastroenterology, The Affiliated Hospital of Qingdao UniversityAbstract Digestive system diseases, including liver diseases, gastrointestinal cancers, and inflammatory bowel diseases, pose major health challenges worldwide. These conditions are influenced by a range of key metabolic signaling pathways, many of which are regulated by palmitoylation. Palmitoylation is a type of lipid modification catalyzed by DHHC palmitoyl S-acyltransferases (DHHC-PTAs) and depalmitoylases, which play critical roles in modulating protein localization, stability, and signal transduction. Dysregulation of S-palmitoylation is closely associated with numerous diseases, including these of the digestive system, through multiple key processes such as immune responses, lipid metabolism, and cellular signaling. Decades of investigations have driven the development of a large body of inhibitors targeting zDHHCs and depalmitoylases, such as S-(2-acetamidoethyl) 2-bromohexadecanethioate (MY-D-4), Artemisinin and Lomitapide. This review provides a comprehensive summary of the role of palmitoylation in digestive system diseases, discusses its effect on disease mechanisms. By elucidating the regulatory functions of palmitoylation under these conditions, this review aimed to identify new strategies for the diagnosis and treatment of digestive system disorders.https://doi.org/10.1038/s41420-025-02629-z
spellingShingle Hanqing Li
Qiuxiang Yuan
Shuangshuang Wang
Tao Yu
Xingsi Qi
Role of S-palmitoylation in digestive system diseases
Cell Death Discovery
title Role of S-palmitoylation in digestive system diseases
title_full Role of S-palmitoylation in digestive system diseases
title_fullStr Role of S-palmitoylation in digestive system diseases
title_full_unstemmed Role of S-palmitoylation in digestive system diseases
title_short Role of S-palmitoylation in digestive system diseases
title_sort role of s palmitoylation in digestive system diseases
url https://doi.org/10.1038/s41420-025-02629-z
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