Related Experiment Video
Updated: Jan 2, 2026
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
The Ubiquitin Code of NODs Signaling Pathways in Health and Disease
Rubén Julio Martínez-Torres1, Mathias Chamaillard1
1University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.
Abstract:
NOD1 and NOD2 belong to the family of intracellular Nod-like receptors (NLRs) that are involved in the maintenance of tissue homeostasis and host defense against bacteria and some viruses. When sensing such microbes, those NLRs act as hitherto scaffolding proteins for activating multiple downstream inflammatory signaling pathways to promote the production of cytokines and chemokines that are ultimately important for pathogen clearance. In recent years, substantial advances have been made on our understanding of a contextual series of intracellular processes that regulate such group of innate immune molecules, including phosphorylation and ubiquitination. Specifically, we will herein discuss those recently described posttranslational modifications of either NOD1 or NOD2 that fundamentally contribute to the robustness of protective responses within specific tissues through either internal domain association or external interactions with various proteins. From a public health perspective, it is then anticipated that a better understanding how genetic mutations and deregulation of these activating and repressing mechanisms might break down in diseases would open up new therapeutic avenues for humanity.
Insights
NOD1 and NOD2, key innate immune sensors, are regulated by posttranslational modifications like phosphorylation and ubiquitination. Understanding these processes offers new therapeutic targets for diseases linked to immune dysregulation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- NOD1 and NOD2 are intracellular Nod-like receptors (NLRs) crucial for tissue homeostasis and host defense.
- These receptors act as scaffolding proteins, initiating inflammatory signaling pathways to combat bacterial and viral infections.
- Recent research highlights the importance of intracellular processes, including phosphorylation and ubiquitination, in regulating NLR function.
Purpose of the Study:
- To discuss recent advances in understanding the posttranslational modifications of NOD1 and NOD2.
- To explore how these modifications impact innate immune responses and tissue-specific protective mechanisms.
- To identify potential therapeutic avenues by understanding disease-related dysregulation of these NLRs.
Main Methods:
- Review of recent scientific literature on NOD1 and NOD2.
- Analysis of studies detailing phosphorylation and ubiquitination of NOD1 and NOD2.
- Discussion of protein-protein interactions and domain associations.
Main Results:
- Posttranslational modifications, specifically phosphorylation and ubiquitination, are critical regulators of NOD1 and NOD2 activity.
- These modifications influence the receptors' scaffolding function and interactions with other proteins.
- Dysregulation of these modification mechanisms can compromise protective immune responses.
Conclusions:
- Posttranslational modifications of NOD1 and NOD2 are fundamental to robust innate immunity.
- A deeper understanding of these regulatory mechanisms and their link to diseases is essential.
- Targeting these pathways presents promising therapeutic strategies for various human diseases.
Related Concept Videos
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
02:04Covalently Linked Protein Regulators
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
01:13The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:18The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
02:18The Proteasome