InTRIMsic immunity: Positive and negative regulation of immune signaling by tripartite motif proteins

• Published in: Cytokine & growth factor reviews Vol. 25; no. 5; pp. 563 - 576
• Main Authors: Versteeg, Gijs A, Benke, Stefan, García-Sastre, Adolfo, Rajsbaum, Ricardo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2014
• Subjects: Adaptor Proteins, Signal Transducing - immunology; Advanced Basic Science; Amino Acid Motifs; Animals; Cytokines - immunology; E3 ligase; Evolution, Molecular; Humans; Immunity, Innate; Interferon; Invertebrates - classification; Membrane Proteins - immunology; Signal Transduction; TRIM protein; TRIMmunity; Ubiquitin; Ubiquitin - immunology; PI3KC2β; TRAF; TRIM; TRIM-ubiquitin body; apoptosis-associated speck-like protein containing a CARD; CLR; MHC; RIG-I; major histocompatibility complex; NS1; TNF; CARD; neural precursor cell expressed developmentally down-regulated 8; myeloid differentiation primary response gene 88; TBK1; RING; TGFβ-activated kinase; Janus kinase; pattern recognition receptor (PRR); dsRNA; IL; T cell receptor; E3 ligase; SeV; macrophage; 3–5 oligo adenylate synthetase; retinoic acid inducible I; TANK-binding kinase; PBMC; mitochondrial antiviral signaling; IRF; TRIF; dendritic cell; stimulator and activator of transcription; DEAD-box protein 41; TRIM protein; IFNα receptor; interferon-stimulated gene; PHD; melanoma differentiation-associated protein 5; ASC; NLR; Absent in melanoma 2; phosphatidylinositol 3 kinase C2β; RLR; ISG; natural killer cell; NFκB essential modulator; IFITM; IFN regulatory factor; interferon-induced transmembrane protein; TGFβ-activated kinase binding protein; IKK; ISG15; ubiquitin; PAMP; MAVS; STAT; IFNαR; TAB; tumor necrosis factor; RING-BBox-coiled coil (= tripartite motif); small ubiquitin-like modifier; PIN1; STING; toll-like receptor; MYD88; DC; TAK; nuclear factor κB; Sendai virus; mouse embryonic fibroblast; DDX41; double-stranded RNA; influenza virus non structural 1; 5′-triphosphate RNA; gene encoding phosphoribosylglycinamide formyltransferase; IκB kinase; PRR; TNF receptor associated factor; prolyl isomerase 1; C-type lectin receptor; iNOS; SUMO; NFκB; Ub; MEF; 5′ppp-RNA; really interesting new gene; AIM2; RBCC; ROS; IFN-stimulated gene 15; GART; NEMO; NK; OAS; TCR; NEDD8; TIR-domain-containing adapter-inducing IFN; MDA5; RIG-I-like receptor; IFN; caspase activation and recruitment domain; tripartite motif protein; TRIMmunity; reactive oxygen species; TLR; interleukin; inducible nitric oxide synthetase; pathogen-associated molecular pattern; TUB; NOD-like receptor; plant homeo domain; interferon; JAK; stimulator of interferon genes; MΦ; peripheral blood mononuclear cell; Ubiquitin; Interferon
• ISSN: 1359-6101; 1879-0305
• DOI: 10.1016/j.cytogfr.2014.08.001

Abstract During the immune response, striking the right balance between positive and negative regulation is critical to effectively mount an anti-microbial defense while preventing detrimental effects from exacerbated immune activation. Intra-cellular immune signaling is tightly regulated by various post-translational modifications, which allow for this dynamic response. One of the post-translational modifiers critical for immune control is ubiquitin, which can be covalently conjugated to lysines in target molecules, thereby altering their functional properties. This is achieved in a process involving E3 ligases which determine ubiquitination target specificity. One of the most prominent E3 ligase families is that of the tripartite motif (TRIM) proteins, which counts over 70 members in humans. Over the last years, various studies have contributed to the notion that many members of this protein family are important immune regulators. Recent studies into the mechanisms by which some of the TRIMs regulate the innate immune system have uncovered important immune regulatory roles of both covalently attached, as well as unanchored poly-ubiquitin chains. This review highlights TRIM evolution, recent findings in TRIM-mediated immune regulation, and provides an outlook to current research hurdles and future directions.