Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

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

doi:10.1038/s41467-023-43945-1

Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

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 PengAnthony Sadler, Dakang Xu

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	8465
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43945-1
State	Published - Dec 2023
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-023-43945-1

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title = "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 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.",

author = "Danfeng Dong and Yuzhang Du and Xuefeng Fei and Hao Yang and Xiaofang Li and Xiaobao Yang and Junrui Ma and Shu Huang and Zhihui Ma and Juanjuan Zheng and Chan, {David W.} and Liyun Shi and Yunqi Li and Irving, {Aaron T.} and Xiangliang Yuan and Xiangfan Liu and Peihua Ni and Yiqun Hu and Guangxun Meng and Yibing Peng and Anthony Sadler and Dakang Xu",

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year = "2023",

month = dec,

doi = "10.1038/s41467-023-43945-1",

language = "English (US)",

volume = "14",

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T1 - Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

AU - Dong, Danfeng

AU - Du, Yuzhang

AU - Fei, Xuefeng

AU - Yang, Hao

AU - Li, Xiaofang

AU - Yang, Xiaobao

AU - Ma, Junrui

AU - Huang, Shu

AU - Ma, Zhihui

AU - Zheng, Juanjuan

AU - Chan, David W.

AU - Shi, Liyun

AU - Li, Yunqi

AU - Irving, Aaron T.

AU - Yuan, Xiangliang

AU - Liu, Xiangfan

AU - Ni, Peihua

AU - Hu, Yiqun

AU - Meng, Guangxun

AU - Peng, Yibing

AU - Sadler, Anthony

AU - Xu, Dakang

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC

Abstract

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