SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1β and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 2 vom: 27. Feb., Seite 113752 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ha, Jihoon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2024.113752 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368314243 |
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| 100 | 1 | |a Ha, Jihoon |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination |
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| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1β and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CUL1 | |
| 650 | 4 | |a K63-linked polyubiquitination | |
| 650 | 4 | |a NLRP3 inflammasome | |
| 650 | 4 | |a SERTAD1 | |
| 650 | 4 | |a autoimmune diseases | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a SERTAD1 protein, human |2 NLM | |
| 650 | 7 | |a Sertad1 protein, mouse |2 NLM | |
| 650 | 7 | |a NLRP3 protein, human |2 NLM | |
| 650 | 7 | |a Nlrp3 protein, mouse |2 NLM | |
| 700 | 1 | |a Kim, Minbeom |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jin Seok |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yerin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jae Young |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Jin-Cheol |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Dongyeob |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Seong Shil |e verfasserin |4 aut | |
| 700 | 1 | |a You, Jiyeon |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Su Myung |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hye Young |e verfasserin |4 aut | |
| 700 | 1 | |a Mizuno, Seiya |e verfasserin |4 aut | |
| 700 | 1 | |a Takahashi, Satoru |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Seong-Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Seok Hee |e verfasserin |4 aut | |
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