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The deubiquitinating enzyme, ubiquitin‐specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein
Author(s) -
Lee Jae Young,
Seo Dongyeob,
You Jiyeon,
Chung Sehee,
Park Jin Seok,
Lee JiHyung,
Jung Su Myung,
Lee Youn Sook,
Park Seok Hee
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12558
Subject(s) - deubiquitinating enzyme , inflammasome , signal transducing adaptor protein , ubiquitin , microbiology and biotechnology , signal transduction , chemistry , caspase 1 , receptor , biology , biochemistry , gene
NOD‐like receptor family protein 3 (NLRP3)‐mediated inflammasome activation promotes caspase‐1‐dependent production of interleukin‐1β ( IL ‐1β) and requires the adaptor protein ASC . Compared with the priming and activation mechanisms of the inflammasome signaling pathway, post‐translational ubiquitination/deubiquitination mechanisms controlling inflammasome activation have not been clearly addressed. We here demonstrate that the deubiquitinating enzyme USP 50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63‐linked polyubiquitination of ASC . USP 50 knockdown in human THP ‐1 cells and mouse bone marrow‐derived macrophages shows a significant decrease in procaspase‐1 cleavage, resulting in a reduced secretion of IL ‐1β and interleukin‐18 ( IL ‐18) upon treatment with NLRP 3 stimuli and a reduction in ASC speck formation and oligomerization. Thus, we elucidate a novel regulatory mechanism of the inflammasome signaling pathway mediated by the USP 50 deubiquitinating enzyme.