Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.
Inflammasome activity is controlled by ZBTB16-dependent SUMOylation of ASC.
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DOI：
10.1038/s41467-023-43945-1
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发表时间：
2023-12-20
影响因子：
16.6
通讯作者：
Xu, Dakang
中科院分区：
文献类型：
--
作者：
Dong, Danfeng;Du, Yuzhang;Fei, Xuefeng;Yang, Hao;Li, Xiaofang;Yang, Xiaobao;Ma, Junrui;Huang, Shu;Ma, Zhihui;Zheng, Juanjuan;Chan, David W.;Shi, Liyun;Li, Yunqi;Irving, Aaron T.;Yuan, Xiangliang;Liu, Xiangfan;Ni, Peihua;Hu, Yiqun;Meng, Guangxun;Peng, Yibing;Sadler, Anthony;Xu, Dakang
炎性体活性对于免疫应答是重要的，并且在许多临床病症中是有用的。在这里，我们确定了一种机制，调节中央Caspase-1和NLR（Nod样受体）衔接蛋白ASC（骨化相关的斑点样蛋白含有CARD）。我们发现ASC在组装炎性小体中的功能是由SUMO（小泛素样修饰剂）修饰控制的，并确定核ZBTB 16（锌指和BTB结构域蛋白16）促进了这种SUMO化。通过在Muckle-Wells综合征的小鼠模型中消融ZBTB 16来减少由组成性过度活跃炎性体引起的急性炎症发病机制，证明了该活性的生理学意义。总之，我们的研究结果确定了ZBTB 16依赖性控制ASC SUMO化组装炎性小体以促进这种促炎反应的进一步机制。炎性小体是多蛋白复合物，包括蛋白ASC，其响应于炎性刺激而组装。在这里，作者阐明了炎性小体形成过程中ASC的调节，并显示了SUMO化和锌指和含BTB结构域的蛋白16（ZBTB 16）的参与。
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. Inflammasomes are multiprotein complexes, including the protein ASC, that assemble in response to inflammatory stimulation. Here the authors characterise the regulation of ASC during inflammasome formation and show the involvement of SUMOylation and zinc-finger and BTB domain-containing protein 16 (ZBTB16).
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影响因子：
7
作者：
Yu, Tae-Geun;Cha, Jeong Seok;Kim, Gijeong;Sohn, Yoo-Kyoung;Yoo, Youngki;Kim, Uijin;Song, Ji-Joon;Cho, Hyun-Soo;Kim, Hak-Sung
通讯作者：
Kim, Hak-Sung
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
DOI：
10.1007/978-1-4939-9055-9_14
发表时间：
2019-01-01
期刊：
POST-TRANSLATIONAL MODIFICATION OF PROTEINS, 3 EDITION
影响因子：
--
作者：
Breucker, Jan;Pichler, Andrea
通讯作者：
Pichler, Andrea
DOI：
10.1007/978-1-4939-3581-9_18
发表时间：
2016-01-01
期刊：
PROGRAMMED CELL DEATH
影响因子：
--
作者：
Kueh, Andrew J.;Herold, Marco J.
通讯作者：
Herold, Marco J.
影响因子：
48
作者：
de Chaumont, Fabrice;Dallongeville, Stephane;Olivo-Marin, Jean-Christophe
通讯作者：
Olivo-Marin, Jean-Christophe