Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC
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Published:2023-12-20
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Dong Danfeng, Du Yuzhang, Fei Xuefeng, Yang Hao, Li Xiaofang, Yang Xiaobao, Ma Junrui, Huang Shu, Ma Zhihui, Zheng Juanjuan, Chan David W.ORCID, Shi Liyun, Li Yunqi, Irving Aaron T.ORCID, Yuan Xiangliang, Liu Xiangfan, Ni Peihua, Hu Yiqun, Meng GuangxunORCID, Peng Yibing, Sadler Anthony, Xu Dakang
Abstract
AbstractInflammasome 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.
Funder
National Natural Science Foundation of China Department of Health | National Health and Medical Research Council
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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