| Autor: |
Danfeng Dong, Yuzhang Du, Xiaofang Li, Xiaobao Yang, Shu Huang, Zhihui Ma, Juanjuan Zheng, David Chan, Liyun Shi, Aaron Irving, Xiangliang Yuan, Xiangfan Liu, Peihua Ni, Yiqun Hu, Guangxun Meng, Yibing Peng, Anthony Sadler, Dakang Xu |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-793134/v1 |
| Popis: |
Inflammasome activity is important for our immune response and is instrumental in numerous clinical conditions. Here we identify a novel control mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that activation and subsequent oligomerization of ASC is controlled by SUMO (small ubiquitin-like modifier) modification and identify that the nuclear ZBTB16 (Zinc finger and BTB domain-containing protein 16) regulates this SUMOylation. Accordingly, ablating ZBTB16 reduces ASC SUMOylation and ensuing inflammasome activity. This mechanism is pivotal as we demonstrate that ablating ZBTB16 relieves acute inflammatory pathogenesis in a murine model of Muckle-Wells syndrome caused by a hyperactive inflammasome. Our findings advance our understanding of inflammasome activity and, by recognizing processes that control the central adaptor molecule, identify new and more comprehensive therapeutic strategies to target pathogenic inflammasome activity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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