期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 47, 页码 -出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.579961
关键词
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资金
- KAKENHI from Japan Society for the Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Global Center of Education and Research for Chemical Biology of the Diseases
- Global Center of Excellence Program (GCOE) Program
- Strategic Research Program for Brain Sciences by MEXT
- Advanced Research for Medical Products Mining Programme of the National Institute of Bio-medical Innovation
- Funding Program for Next Generation World-leading Researchers
- Nagase Science and Technology Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [26293011, 26114009, 25650061] Funding Source: KAKEN
Lysosome rupture triggers NLRP3 inflammasome activation in macrophages. However, the underlying mechanism is not fully understood. Here we showed that the TAK1-JNK pathway, a MAPK signaling pathway, is activated through lysosome rupture and that this activation is necessary for the complete activation of the NLRP3 inflammasome through the oligomerization of an adapter protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). We also revealed that the activation of the TAK1-JNK pathway is sustained through Ca2+ ions and that calcium/calmodulin-dependent protein kinase type II functions upstream of the TAK1-JNK pathway and specifically regulates lysosome rupture-induced NLRP3 inflammasome activation. These data suggest a novel role for the TAK1-JNK pathway as a critical regulator of NLRP3 inflammasome activation.
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