The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response?
Recognition of danger signals by a cell initiates a powerful cascade of events generally leading to inflammation. Inflammatory caspases and several other proteases become activated and subsequently cleave their target proinflammatory mediators. The irreversible nature of this process implies that th...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/6/903 |
| _version_ | 1797565403148320768 |
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| author | Dominique Leboeuf Maxim Pyatkov Timofei S. Zatsepin Konstantin Piatkov |
| author_facet | Dominique Leboeuf Maxim Pyatkov Timofei S. Zatsepin Konstantin Piatkov |
| author_sort | Dominique Leboeuf |
| collection | DOAJ |
| description | Recognition of danger signals by a cell initiates a powerful cascade of events generally leading to inflammation. Inflammatory caspases and several other proteases become activated and subsequently cleave their target proinflammatory mediators. The irreversible nature of this process implies that the newly generated proinflammatory fragments need to be sequestered, inhibited, or degraded in order to cancel the proinflammatory program or prevent chronic inflammation. The Arg/N-degron pathway is a ubiquitin-dependent proteolytic pathway that specifically degrades protein fragments bearing N-degrons, or destabilizing residues, which are recognized by the E3 ligases of the pathway. Here, we report that the Arg/N-degron pathway selectively degrades a number of proinflammatory fragments, including some activated inflammatory caspases, contributing in tuning inflammatory processes. Partial ablation of the Arg/N-degron pathway greatly increases IL-1β secretion, indicating the importance of this ubiquitous pathway in the initiation and resolution of inflammation. Thus, we propose a model wherein the Arg/N-degron pathway participates in the control of inflammation in two ways: in the generation of inflammatory signals by the degradation of inhibitory anti-inflammatory domains and as an “off switch” for inflammatory responses through the selective degradation of proinflammatory fragments. |
| first_indexed | 2024-03-10T19:11:40Z |
| format | Article |
| id | doaj.art-fd55a077d9c3496ea2c243cd33ba1cba |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:11:40Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-fd55a077d9c3496ea2c243cd33ba1cba2023-11-20T03:46:17ZengMDPI AGBiomolecules2218-273X2020-06-0110690310.3390/biom10060903The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response?Dominique Leboeuf0Maxim Pyatkov1Timofei S. Zatsepin2Konstantin Piatkov3Skolkovo Institute of Science and Technology, 121205 Moscow, RussiaInstitute of Mathematical Problems of Biology, Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, Pushchino, 142290 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 121205 Moscow, RussiaRecognition of danger signals by a cell initiates a powerful cascade of events generally leading to inflammation. Inflammatory caspases and several other proteases become activated and subsequently cleave their target proinflammatory mediators. The irreversible nature of this process implies that the newly generated proinflammatory fragments need to be sequestered, inhibited, or degraded in order to cancel the proinflammatory program or prevent chronic inflammation. The Arg/N-degron pathway is a ubiquitin-dependent proteolytic pathway that specifically degrades protein fragments bearing N-degrons, or destabilizing residues, which are recognized by the E3 ligases of the pathway. Here, we report that the Arg/N-degron pathway selectively degrades a number of proinflammatory fragments, including some activated inflammatory caspases, contributing in tuning inflammatory processes. Partial ablation of the Arg/N-degron pathway greatly increases IL-1β secretion, indicating the importance of this ubiquitous pathway in the initiation and resolution of inflammation. Thus, we propose a model wherein the Arg/N-degron pathway participates in the control of inflammation in two ways: in the generation of inflammatory signals by the degradation of inhibitory anti-inflammatory domains and as an “off switch” for inflammatory responses through the selective degradation of proinflammatory fragments.https://www.mdpi.com/2218-273X/10/6/903Arg/N-degron pathwayUBR-ubiquitin ligasesubiquitinproteolysisinflammatory caspasesinflammation |
| spellingShingle | Dominique Leboeuf Maxim Pyatkov Timofei S. Zatsepin Konstantin Piatkov The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? Biomolecules Arg/N-degron pathway UBR-ubiquitin ligases ubiquitin proteolysis inflammatory caspases inflammation |
| title | The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? |
| title_full | The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? |
| title_fullStr | The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? |
| title_full_unstemmed | The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? |
| title_short | The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response? |
| title_sort | arg n degron pathway a potential running back in fine tuning the inflammatory response |
| topic | Arg/N-degron pathway UBR-ubiquitin ligases ubiquitin proteolysis inflammatory caspases inflammation |
| url | https://www.mdpi.com/2218-273X/10/6/903 |
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