4.5 Article

The APC10 subunit of the anaphase-promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle

期刊

FEBS LETTERS
卷 595, 期 19, 页码 2463-2478

出版社

WILEY
DOI: 10.1002/1873-3468.14181

关键词

anaphase-promoting complex subunit 10; cell cycle; cell synchronization; NLR family; NLRP3 inflammasome; proinflammatory cytokines; PYRIN domain containing-3

资金

  1. National Natural Science Foundation of China [81730061]
  2. Guangdong Province 'Pearl River Talent Plan' Innovation and Entrepreneurship Team Project [2017ZT07Y580]

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The study reveals that APC10 is a critical mediator in regulating NLRP3 inflammasome activation during the cell cycle, acting as a switch by interacting with NLRP3 to either promote or repress inflammatory responses.
The activation of the NLRP3 inflammasome plays a crucial role in the innate immune response. During cell division, NLRP3 inflammasome activation must be strictly controlled. In this study, we discover that the anaphase-promoting complex subunit 10 (APC10), a substrate recognition protein of the anaphase-promoting complex/cyclosome (APC/C), is a critical mediator of NLRP3 inflammasome activation. During interphase, APC10 interacts with NLRP3 to promote NLRP3 inflammasome activation, whereas during mitosis, APC10 disassociates from the NLRP3 inflammasome to repress inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch for NLRP3 inflammasome activation during the cell cycle.

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