Journal Article Review Epublish
PubMed: 40305291 DOI: 10.3390/biom15040549
The Role of Post-Translational Modifications in Necroptosis.
Biomolecules 15(4)
Authors: Hao Xiao, Zeping Han, Min Xu, Xukang Gao, Shuangjian Qiu, Ning Ren, Yong Yi, Chenhao Zhou
Affiliations
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, 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.
MeSH
Necroptosis, Protein Processing, Post-Translational, Therapeutics