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Updated: Jul 5, 2025

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
Published on: February 27, 2020
Post-translational modulation of cell signalling through protein succinylation
Katharina F Kubatzky1,2, Yue Gao1,2, Dayoung Yu1,2
1Department of Infectious Diseases, Medical Faculty Heidelberg, Medical Microbiology and Hygiene, Heidelberg University, 69120 Heidelberg, Germany.
Cells use post-translational modifications (PTMs) to regulate protein activity. This review focuses on succinylation, a PTM where tricarboxylic acid cycle metabolites modify proteins, impacting health and disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Cells respond to signals via receptors and downstream proteins, modulating gene transcription.
- Post-translational modifications (PTMs) are crucial for fine-tuning protein activity.
- Metabolites from the tricarboxylic acid (TCA) cycle can act as PTMs, modifying proteins.
Purpose of the Study:
- To review the process of protein succinylation.
- To highlight the role of succinylation in health and disease.
- To explore the link between metabolic states and PTMs.
Main Methods:
- Literature review of PTMs, TCA cycle metabolites, and succinylation.
- Analysis of the role of succinate as a signaling molecule and PTM.
- Examination of the Warburg effect and its metabolic consequences.
Main Results:
- Metabolites like acetate, succinate, and lactate can modify lysine residues on proteins.
- Succinate acts as a signaling molecule through GPR91 and protein succinylation.
- The Warburg effect leads to metabolite accumulation, including succinate, impacting cellular function.
Conclusions:
- Protein succinylation is a critical PTM regulated by TCA cycle metabolites.
- Succinylation plays a significant role in cellular metabolism, aging, and diseases like cancer.
- Understanding succinylation offers insights into metabolic regulation and therapeutic strategies.
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