The Role of Post-Translational Modifications in Necroptosis

Necroptosis, a distinct form of regulated necrosis implicated in various human pathologies, is orchestrated through sophisticated signaling pathways. During this process, cells undergoing necroptosis exhibit characteristic necrotic morphology and provoke substantial inflammatory responses. Post-tran...

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Main Authors: Hao Xiao, Zeping Han, Min Xu, Xukang Gao, Shuangjian Qiu, Ning Ren, Yong Yi, Chenhao Zhou
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/4/549
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author Hao Xiao
Zeping Han
Min Xu
Xukang Gao
Shuangjian Qiu
Ning Ren
Yong Yi
Chenhao Zhou
author_facet Hao Xiao
Zeping Han
Min Xu
Xukang Gao
Shuangjian Qiu
Ning Ren
Yong Yi
Chenhao Zhou
author_sort Hao Xiao
collection DOAJ
description Necroptosis, a distinct form of regulated necrosis implicated in various human pathologies, is orchestrated through sophisticated signaling pathways. During this process, cells undergoing necroptosis exhibit characteristic necrotic morphology and provoke substantial inflammatory responses. Post-translational modifications (PTMs)—chemical alterations occurring after protein synthesis that critically regulate protein functionality—constitute essential regulatory components within these complex signaling cascades. This intricate crosstalk between necroptotic pathways and PTM networks presents promising therapeutic opportunities. Our comprehensive review systematically analyzes the molecular mechanisms underlying necroptosis, with particular emphasis on the regulatory roles of PTMs in signal transduction. Through systematic evaluation of key modifications including ubiquitination, phosphorylation, glycosylation, methylation, acetylation, disulfide bond formation, caspase cleavage, nitrosylation, and SUMOylation, we examine potential therapeutic applications targeting necroptosis in disease pathogenesis. Furthermore, we synthesize current pharmacological strategies for manipulating PTM-regulated necroptosis, offering novel perspectives on clinical target development and therapeutic intervention.
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series Biomolecules
spelling doaj-art-edd3113644e24f1e86cd8fdc56e879212025-08-20T02:24:42ZengMDPI AGBiomolecules2218-273X2025-04-0115454910.3390/biom15040549The Role of Post-Translational Modifications in NecroptosisHao Xiao0Zeping Han1Min Xu2Xukang Gao3Shuangjian Qiu4Ning Ren5Yong Yi6Chenhao Zhou7Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaNecroptosis, a distinct form of regulated necrosis implicated in various human pathologies, is orchestrated through sophisticated signaling pathways. During this process, cells undergoing necroptosis exhibit characteristic necrotic morphology and provoke substantial inflammatory responses. Post-translational modifications (PTMs)—chemical alterations occurring after protein synthesis that critically regulate protein functionality—constitute essential regulatory components within these complex signaling cascades. This intricate crosstalk between necroptotic pathways and PTM networks presents promising therapeutic opportunities. Our comprehensive review systematically analyzes the molecular mechanisms underlying necroptosis, with particular emphasis on the regulatory roles of PTMs in signal transduction. Through systematic evaluation of key modifications including ubiquitination, phosphorylation, glycosylation, methylation, acetylation, disulfide bond formation, caspase cleavage, nitrosylation, and SUMOylation, we examine potential therapeutic applications targeting necroptosis in disease pathogenesis. Furthermore, we synthesize current pharmacological strategies for manipulating PTM-regulated necroptosis, offering novel perspectives on clinical target development and therapeutic intervention.https://www.mdpi.com/2218-273X/15/4/549necroptosispost-translational modifications (PTMs)targeted therapymechanism
spellingShingle Hao Xiao
Zeping Han
Min Xu
Xukang Gao
Shuangjian Qiu
Ning Ren
Yong Yi
Chenhao Zhou
The Role of Post-Translational Modifications in Necroptosis
Biomolecules
necroptosis
post-translational modifications (PTMs)
targeted therapy
mechanism
title The Role of Post-Translational Modifications in Necroptosis
title_full The Role of Post-Translational Modifications in Necroptosis
title_fullStr The Role of Post-Translational Modifications in Necroptosis
title_full_unstemmed The Role of Post-Translational Modifications in Necroptosis
title_short The Role of Post-Translational Modifications in Necroptosis
title_sort role of post translational modifications in necroptosis
topic necroptosis
post-translational modifications (PTMs)
targeted therapy
mechanism
url https://www.mdpi.com/2218-273X/15/4/549
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