Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC
Abstract Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We s...
| 發表在: | Nature Communications |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
| 格式: | Article |
| 語言: | 英语 |
| 出版: |
Nature Portfolio
2023-12-01
|
| 在線閱讀: | https://doi.org/10.1038/s41467-023-43945-1 |
| _version_ | 1852665669279023104 |
|---|---|
| author | Danfeng Dong Yuzhang Du Xuefeng Fei Hao Yang Xiaofang Li Xiaobao Yang Junrui Ma Shu Huang Zhihui Ma Juanjuan Zheng David W. Chan Liyun Shi Yunqi Li Aaron T. Irving Xiangliang Yuan Xiangfan Liu Peihua Ni Yiqun Hu Guangxun Meng Yibing Peng Anthony Sadler Dakang Xu |
| author_facet | Danfeng Dong Yuzhang Du Xuefeng Fei Hao Yang Xiaofang Li Xiaobao Yang Junrui Ma Shu Huang Zhihui Ma Juanjuan Zheng David W. Chan Liyun Shi Yunqi Li Aaron T. Irving Xiangliang Yuan Xiangfan Liu Peihua Ni Yiqun Hu Guangxun Meng Yibing Peng Anthony Sadler Dakang Xu |
| author_sort | Danfeng Dong |
| collection | DOAJ |
| container_title | Nature Communications |
| description | Abstract Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a 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 the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response. |
| format | Article |
| id | doaj-art-7f19608cb89141d283f2dcd9b36f3fb4 |
| institution | Directory of Open Access Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| spelling | doaj-art-7f19608cb89141d283f2dcd9b36f3fb42025-08-19T21:35:19ZengNature PortfolioNature Communications2041-17232023-12-0114111610.1038/s41467-023-43945-1Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASCDanfeng Dong0Yuzhang Du1Xuefeng Fei2Hao Yang3Xiaofang Li4Xiaobao Yang5Junrui Ma6Shu Huang7Zhihui Ma8Juanjuan Zheng9David W. Chan10Liyun Shi11Yunqi Li12Aaron T. Irving13Xiangliang Yuan14Xiangfan Liu15Peihua Ni16Yiqun Hu17Guangxun Meng18Yibing Peng19Anthony Sadler20Dakang Xu21Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAssisted Reproduction Center, Northwest Women’s and Children’s HospitalDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineSchool of Medicine, The Chinese University of Hong Kong-ShenzhenDepartment of Microbiology and Immunology, Nanjing University of Chinese MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Laboratory Studies, Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineThe Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection, University of Chinese Academy of SciencesDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical ResearchDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a 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 the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.https://doi.org/10.1038/s41467-023-43945-1 |
| spellingShingle | Danfeng Dong Yuzhang Du Xuefeng Fei Hao Yang Xiaofang Li Xiaobao Yang Junrui Ma Shu Huang Zhihui Ma Juanjuan Zheng David W. Chan Liyun Shi Yunqi Li Aaron T. Irving Xiangliang Yuan Xiangfan Liu Peihua Ni Yiqun Hu Guangxun Meng Yibing Peng Anthony Sadler Dakang Xu Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title | Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title_full | Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title_fullStr | Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title_full_unstemmed | Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title_short | Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC |
| title_sort | inflammasome activity is controlled by zbtb16 dependent sumoylation of asc |
| url | https://doi.org/10.1038/s41467-023-43945-1 |
| work_keys_str_mv | AT danfengdong inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT yuzhangdu inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT xuefengfei inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT haoyang inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT xiaofangli inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT xiaobaoyang inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT junruima inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT shuhuang inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT zhihuima inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT juanjuanzheng inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT davidwchan inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT liyunshi inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT yunqili inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT aarontirving inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT xiangliangyuan inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT xiangfanliu inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT peihuani inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT yiqunhu inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT guangxunmeng inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT yibingpeng inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT anthonysadler inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc AT dakangxu inflammasomeactivityiscontrolledbyzbtb16dependentsumoylationofasc |