Ubc13 Promotes K63-Linked Polyubiquitination of NLRP3 to Activate Inflammasome

نویسندگان

چکیده

Abstract NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of has been shown to be essential for its activation, yet the functions Ubc13, K63-linked specific ubiquitin-conjugating enzyme E2, activation are not known. In this study, we found that mouse macrophages, Ubc13 knockdown or knockout dramatically impaired activation. Catalytic activity is required control pharmacological inhibitor significantly attenuates Mechanistically, associates with promotes polyubiquitination. Through mass spectrum biochemical analysis, identified lysine 565 687 as theK63-linked polyubiquitination sites NLRP3. Collectively, our data suggest potentiates via promoting site-specific ubiquitination Our study sheds light on mechanisms identifies targeting could effective therapeutic strategy treating aberrant activation–induced pathogenesis.

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2021

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.2001178