Novel Post-Translational Modifications in Macrophages

Macrophages possess a diverse array of mechanisms to regulate their functions and adapt to the ever-changing microenvironment. One such mechanism that has recently garnered significant attention is post-translational modifications (PTMs).

Here, Creative Biolabs shares some knowledge of novel post-translational modifications in macrophages, shedding light on their impact on macrophage biology and their potential implications in various diseases.

Post-Translational Modifications in Macrophages

PTMs are enzymatic or non-enzymatic alterations that occur on proteins following their synthesis. These modifications can profoundly influence protein structure, function, stability, localization, and interactions with other molecules. Traditionally recognized PTMs, such as phosphorylation, acetylation, and ubiquitination, have been extensively studied in macrophages. However, recent discoveries have unearthed an intriguing array of novel PTMs that expand our understanding of macrophage biology.

• Glycosylation. Some studies have highlighted the role of glycosylation in regulating macrophage polarization and immune responses.
• Sumoylation. Recent findings have unraveled the role of sumoylation in fine-tuning macrophage responses, including phagocytosis, inflammatory signaling, and antiviral defense.
• Methylation. Methylation of arginine and lysine residues in histones and non-histone proteins can dynamically regulate macrophage polarization, inflammatory responses, and immune tolerance.
• NEDDylation. NEDDylation plays a crucial role in regulating macrophage activation, inflammasome signaling, and inflammatory diseases.

Novel Post-Translational Modifications on Lysine Mediated by Itaconic Acid: Itaconation

Itaconate, a class of small molecules of endogenous metabolites that have been found to have immunomodulatory activity in recent years, has been found to be produced in large quantities in macrophages following stimulation by pathogenic bacteria. The PTM involved in itaconate is also known as itaconation.

Fig. 1 Endogenous metabolite itaconic acid produces acylation modifications in the lysine side chain of proteins by generating itaconic coenzyme A. (Liu D, et al., 2023)

• Recently, using an antibody "off-target" enrichment combined with an open search strategy, researchers have identified a itaconic acid-mediated itaconation on lysine in macrophages.
• After stimulation of macrophages with bacterial surface antigen mimics in the study, there was a significant increase in the levels of both itaconic coenzyme A and itaconation.
• Site identification revealed that the itaconation may have epigenetic regulation and modulation of the glycolytic pathway.

Application of Post-Translational Modifications in Macrophages

• The discovery of novel PTMs in macrophages has unveiled a new dimension of complexity in their biology.
• emerging PTMs have demonstrated their pivotal roles in modulating macrophage functions, immune responses, and disease pathogenesis.
• Understanding the mechanisms and consequences of these modifications opens up exciting avenues for therapeutic interventions targeting macrophage-driven diseases.

As the mysteries of macrophage PTMs continue to be unraveled, scientists will gain a deeper understanding of immune regulation and potentially revolutionize macrophage therapeutic strategies. To learn more about related services, please contact us.

References

1. Olszowy P, et al. Profiling post-translational modifications of histones in human monocyte-derived macrophages. Proteome Science, 2015, 13(1): 1-13.
2. Liu D, et al. Discovery of Itaconate-Mediated Lysine Acylation. Journal of the American Chemical Society, 2023.