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Merck
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  • The deubiquitinase STAMBP modulates cytokine secretion through the NLRP3 inflammasome.

The deubiquitinase STAMBP modulates cytokine secretion through the NLRP3 inflammasome.

Cellular signalling (2020-12-01)
Joseph S Bednash, Finny Johns, Niharika Patel, Taylor R Smail, James D Londino, Rama K Mallampalli
摘要

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is a multimeric, cytoplasmic, protein complex that regulates maturation and secretion of interleukin (IL)-1β, a potent pro-inflammatory cytokine. Critical to host defense against pathogens, IL-1β amplifies early innate immune responses by activating transcription of numerous other cytokines and chemokines. Excessive IL-1β is associated with poor outcomes in inflammatory illnesses, such as sepsis and the acute respiratory distress syndrome (ARDS). Tight regulation of this signaling axis is vital, but little is known about mechanisms to limit excessive inflammasome activity. Here we identify the deubiquitinase STAM-binding protein (STAMBP) as a negative regulator of the NLRP3 inflammasome. In monocytes, knockout of STAMBP by CRISPR/Cas9 gene editing increased expression of numerous cytokines and chemokines in response to Toll-like receptor (TLR) agonists or bacterial lipopolysaccharide (LPS). This exaggerated inflammatory response was dependent on IL-1β signaling, and STAMBP knockout directly increased release of IL-1β with TLR ligation. While STAMBP does not modulate NLRP3 protein abundance, cellular depletion of the deubiquitinase increased NLRP3 K63 chain polyubiquitination resulting in increased NLRP3 inflammasome activation. These findings describe a unique mechanism of non-degradative ubiquitination of NLRP3 by STAMBP to limit excessive inflammasome activation and to reduce injurious IL-1β signaling.

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Millipore
抗-FLAG® M2磁珠, affinity isolated antibody
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Sigma-Aldrich
脂多糖 来源于大肠杆菌 0111:B4, γ-irradiated, BioXtra, suitable for cell culture
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货号包装规格是否有货价格数量
1 vial
预计发货时间 2025年4月07日
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¥11,580.66