Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.
Danfeng DongYuzhang DuXuefeng FeiHao YangXiaofang LiXiaobao YangJunrui MaShu HuangZhihui MaJuanjuan ZhengDavid Wai ChanLiyun ShiYunqi LiAaron Trent IrvingXiangliang YuanXiangfan LiuPeihua NiYiqun HuGuang-Xun MengYibing PengAnthony SadlerDakang XuPublished in: Nature communications (2023)
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.
Keyphrases
- inflammatory response
- immune response
- nlrp inflammasome
- mouse model
- oxidative stress
- cell death
- binding protein
- protein protein
- liver failure
- small molecule
- endoplasmic reticulum stress
- amino acid
- signaling pathway
- respiratory failure
- extracorporeal membrane oxygenation
- acute respiratory distress syndrome
- aortic dissection