HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction
	Cheng, Z; Huang, MB; Li, W; Hou, L; Jin, L; Fan, QJ; Zhang, LQ; Li, CB; Zeng, L; Yang, CY; Liang, B; Li, FB; Chen, CS
	2024
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	15 期号:1
摘要	The NLRP3 inflammasome plays an important role in protecting the host from infection and aseptic inflammation, and its regulatory mechanism is not completely understood. Dysregulation of NLRP3 can cause diverse inflammatory diseases. HECTD3 is a E3 ubiquitin ligase of the HECT family that has been reported to participate in autoimmune and infectious diseases. However, the relationship between HECTD3 and the NLRP3 inflammasome has not been well studied. Herein, we show that HECTD3 blocks the interaction between NEK7 and NLRP3 to inhibit NLRP3 inflammasome assembly and activation. In BMDMs, Hectd3 deficiency promotes the assembly and activation of NLRP3 inflammasome and the secretion of IL-1 beta, while the overexpression of HECTD3 inhibits these processes. Unexpectedly, HECTD3 functions in an E3 activity independent manner. Mechanically, the DOC domain of HECTD3 interacts with NACHT/LRR domain of NLRP3, which blocks NLRP3-NEK7 interaction and NLRP3 oligomerization. Furthermore, HECTD3 inhibits monosodium urate crystals (MSU)-induced gouty arthritis, a NLRP3-related disease. Thus, we reveal a novel regulatory mechanism of NLRP3 by HECTD3 and suggest HECTD3 could be a potential therapeutic target for NLRP3-dependent pathologies.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14225
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Cheng, Z,Huang, MB,Li, W,et al. HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction[J]. CELL DEATH & DISEASE,2024,15(1).
APA	Cheng, Z.,Huang, MB.,Li, W.,Hou, L.,Jin, L.,...&Chen, CS.(2024).HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction.CELL DEATH & DISEASE,15(1).
MLA	Cheng, Z,et al."HECTD3 inhibits NLRP3 inflammasome assembly and activation by blocking NLRP3-NEK7 interaction".CELL DEATH & DISEASE 15.1(2024).

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