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Updated: May 15, 2025

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
The Role of Post-Translational Modifications in Necroptosis
Hao Xiao1,2,3, Zeping Han1,2,3, Min Xu1,2,3
1Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract:
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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