In:
FEBS Letters, Wiley, Vol. 591, No. 3 ( 2017-02), p. 479-490
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1002/feb2.2017.591.issue-3
DOI:
10.1002/1873-3468.12558
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1460391-3
SSG:
12
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