Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome. Issue 22 (10th November 2017)

• Record Type: Journal Article
• Authors: Kattah, Michael G.; Malynn, Barbara A.; Ma, Averil
• Is Part Of: Journal of molecular biology. Volume 429:Issue 22(2017)
• Page Start: 3471
• Page End: 3485
• Publication Date: 2017-11-10
• Subjects: DUBs deubiquitinases -- IL interleukin -- LUBAC linear ubiquitin assembly complex -- PRRs pattern-recognition receptors -- TLRs Toll-like receptors -- LPS lipopolysaccharide -- NLR nucleotide-binding oligomerization domain-like receptor -- PYD pyrin domain -- NEK7 NIMA-related kinase 7 -- ASC apoptosis-associated speck-like -- BMDMs bone marrow-derived macrophages -- IP immunoprecipitation -- BRCC3 BRCA1/BRAC2 containing complex, subunit 3 -- DSS dextran sodium sulfate -- DA dopamine -- DRD1 dopamine D1 receptor -- PKA protein kinase A -- EPEC enteropathogenic Escherichia coli; NLRP3 inflammasomes -- ubiquitination -- DUB -- E3 ubiquitin ligases -- inflammation; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.10.001
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1β and IL-18. Inflammasome activation is critical for the host's defense against pathogens, but dysregulation of inflammasomes may contribute to the pathogenesis of multiple diseases. Ultimately, understanding how various ubiquitin interacting proteins control inflammatory signaling cascades could provide new pathways for therapeutic intervention. Here we review specific ubiquitin-modifying enzymes and ubiquitination events that orchestrate inflammatory responses, with an emphasis on the NLRP3 inflammasome. Graphical Abstract: Highlights: Ubiquitin-modifying enzymes play critical roles in inflammatory signaling cascades. The NLRP3 inflammasome is a prime example of ubiquitin-mediated regulation. Each component of the NLRP3 inflammasome undergoes ubiquitin modification. Despite challenges, ubiquitin-modifying enzymes could be important drug targets.