Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

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...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43945-1
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Summary: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.
ISSN:2041-1723

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