TY - JOUR
T1 - TRIM21 regulates pyroptotic cell death by promoting Gasdermin D oligomerization
AU - Gao, Wenqing
AU - Li, Yuanyuan
AU - Liu, Xuehe
AU - Wang, Sen
AU - Mei, Pucheng
AU - Chen, Zijun
AU - Liu, Kewei
AU - Li, Suhua
AU - Xu, Xue Wei
AU - Gan, Jianhua
AU - Wu, Jiaxue
AU - Ji, Chaoneng
AU - Ding, Chen
AU - Liu, Xing
AU - Lai, Yuping
AU - He, Housheng Hansen
AU - Lieberman, Judy
AU - Wu, Hao
AU - Chen, Xiangjun
AU - Li, Jixi
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.
PY - 2022/2
Y1 - 2022/2
N2 - Gasdermin-D (GSDMD), the executioner of pyroptotic cell death when it is cleaved by inflammatory caspases, plays a crucial role in host defense and the response to danger signals. So far, there are no known mechanisms, other than cleavage, for regulating GSDMD. Here, we show that tripartite motif protein TRIM21 acts as a positive regulator of GSDMD-dependent pyroptosis. TRIM21 interacted with GSDMD via its PRY-SPRY domain, maintaining GSDMD stable expression in resting cells yet inducing the N-terminus of GSDMD (GSDMD-N) aggregation during pyroptosis. TRIM21-deficient cells displayed a reduced cell death in response to NLRP3 or NLRC4 inflammasome activation. Genetic ablation of TRIM21 in mice conferred protection from LPS-induced inflammation and dextran sulfate sodium-induced colitis. Therefore, TRIM21 plays an essential role in GSDMD-mediated pyroptosis and may be a viable target for controlling and treating inflammation-associated diseases.
AB - Gasdermin-D (GSDMD), the executioner of pyroptotic cell death when it is cleaved by inflammatory caspases, plays a crucial role in host defense and the response to danger signals. So far, there are no known mechanisms, other than cleavage, for regulating GSDMD. Here, we show that tripartite motif protein TRIM21 acts as a positive regulator of GSDMD-dependent pyroptosis. TRIM21 interacted with GSDMD via its PRY-SPRY domain, maintaining GSDMD stable expression in resting cells yet inducing the N-terminus of GSDMD (GSDMD-N) aggregation during pyroptosis. TRIM21-deficient cells displayed a reduced cell death in response to NLRP3 or NLRC4 inflammasome activation. Genetic ablation of TRIM21 in mice conferred protection from LPS-induced inflammation and dextran sulfate sodium-induced colitis. Therefore, TRIM21 plays an essential role in GSDMD-mediated pyroptosis and may be a viable target for controlling and treating inflammation-associated diseases.
UR - https://www.scopus.com/pages/publications/85114769415
U2 - 10.1038/s41418-021-00867-z
DO - 10.1038/s41418-021-00867-z
M3 - 文章
C2 - 34511601
AN - SCOPUS:85114769415
SN - 1350-9047
VL - 29
SP - 439
EP - 450
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 2
ER -