USP21 Deubiquitinase Regulates AIM2 Inflammasome Activation
| Autor: | Yujin Hong, Kwonyoon Kang, Seong-Ok Lee, Dongyoung Kim, Jeongmin Ryoo, Changhoon Oh, Kwangseog Ahn |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Inflammasomes
THP-1 Cells Immunology Deubiquitinating enzyme AIM2 Immune system Ubiquitin medicine Humans Immunology and Allergy Macrophage RNA Small Interfering Inflammation Innate immune system biology Protein Stability Chemistry Macrophages Ubiquitination Inflammasome Immunity Innate Cell biology DNA-Binding Proteins HEK293 Cells Gene Expression Regulation biology.protein Ubiquitin Thiolesterase Protein Binding Deubiquitination medicine.drug |
| Zdroj: | The Journal of Immunology. 207:1926-1936 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2100449 |
| Popis: | Innate immune sensing of cytosolic DNA via absent in melanoma 2 (AIM2) is a key mechanism leading to inflammatory responses. As aberrant immune responses by dysregulated AIM2 are associated with autoinflammatory diseases, activation of the AIM2 inflammasome should be tightly controlled. In this study, we discovered that ubiquitination and deubiquitination of AIM2 are critical events that regulate AIM2 inflammasome activation. In resting human macrophage cells, AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation to avoid autoinflammation. Upon DNA stimulation, USP21 binds to AIM2 and deubiquitinates it, thereby increasing its protein stability. In addition to the role of USP21 in regulating AIM2 turnover, we uncovered that USP21-mediated deubiquitination of AIM2 is required for the assembly of the AIM2 inflammasome. Depletion of USP21 does not affect the DNA-binding ability of AIM2 but inhibits the formation of the AIM2–ASC complex. Our findings establish that fine-tuning of AIM2 by the ubiquitin system is important for regulating AIM2 inflammasome activation. |
| Databáze: | OpenAIRE |
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