TRIM family proteins and their emerging roles in innate immunity

Ozato, Keiko; Shin, Dong‐Mi; Chang, Tsung-Hsien; Morse, Herbert C.

doi:10.1038/nri2413

Cited by 897 publications

(908 citation statements)

References 129 publications

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“…The overexpression of SVEP1 in our mussels in response to higher metal concentrations illustrates the complexity of the immune response amongst bivalve species. This alteration of the immune response is also suggested by the change in expression of two key regulators of the response to pathogens: a complement factor H homolog (Ferreira et al 2010) and a tripartite motif-containing (TRIM) protein (Ozato et al 2008). Trace metals and organic xenobiotics are typical classes of environmental pollutants with prooxidant effects (Regoli and Giuliani 2014).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

Bertucci

Pierron

Thébault

et al. 2017

Environ Sci Pollut Res

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The freshwater pearl mussel Margaritifera margaritifera is one of the most threatened freshwater bivalves worldwide. In this study, we aimed (i) to study the processes by which water quality might affect freshwater mussels in situ and (ii) to provide insights into the ecotoxicological significance of water pollution to natural populations in order to provide necessary information to enhance conservation strategies. M. margaritifera specimens were sampled in two close sites located upstream or downstream from an illegal dumping site. The renal transcriptome of these animals was assembled and gene transcription determined by RNA-seq. Correlations between transcription levels of each single transcript and the bioaccumulation of nine trace metals, age (estimated by sclerochronology), and condition index were determined in order to identify genes likely to respond to a specific factor. Amongst the studied metals, Cr, Zn, Cd, and Ni were the main factors correlated with transcription levels, with effects on translation, apoptosis, immune response, response to stimulus, and transport pathways.However, the main factor explaining changes in gene transcription appeared to be the age of individuals with a negative correlation with the transcription of retrotransposon-related genes. To investigate this effect further, mussels were classified into three age classes. In young, middle-aged and old animals, transcription levels were mainly explained by Cu, Zn and age, respectively. This suggests differences in the molecular responses of this species to metals during its lifetime that must be better assessed in future ecotoxicology studies.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

Bertucci

Pierron

Thébault

et al. 2017

Environ Sci Pollut Res

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“…9 The tripartite motif (TRIM) family of proteins is defined by the highly conserved RBCC signature domain, which contains a RING finger domain, one or two B-Box domains, and a coiledcoil domain. 10,11 The RING finger domain contains a specialized zinc finger and functions as a ubiquitin protein ligase, either alone or as a part of a multi-subunit E3 protein complex. The associated B-Box and coiled-coil domains are involved in protein interactions and homo/heterodimerization.…”

Section: Introductionmentioning

confidence: 99%

“…TRIM proteins are involved in a variety of cellular functions, including apoptosis, transcription, differentiation and regulation of cell cycle progression. 10,11 In addition, some TRIM proteins exhibit anti-viral activity and may be involved in innate immunity. 10,11 Many TRIM proteins have recently emerged as IFN-induced proteins involved in various cellular processes, including cell proliferation and antiviral activities.…”

Section: Introductionmentioning

confidence: 99%

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

et al. 2015

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TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNa therapy. During the first 24 h following the initiation of IFNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNa-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNa treatment and plays an important role in controlling HCV replication in vitro.

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“…TRIM proteins are involved in a various biological processes [3,4]. TRIM25, also known as estrogen-responsive finger protein (EFP), induces type I IFN production and NF-B activity through the conjugation of a lysine 63-linked polyubiquitin chain to RIG-I [5].…”

Section: Introductionmentioning

confidence: 99%

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Kondo

Watanabe

Hatakeyama

2012

Biochemical and Biophysical Research Communications

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Innate immune responses are triggered by pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) and then activate intracellular signaling pathways including NF-B and interferon regulatory factors. Recently, it has been reported that tripartite motif (TRIM) proteins function as crucial regulators via ubiquitin-mediated modifications for these signaling pathways. In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. Luciferase reporter assays using reporter plasmids including NF-B responsive element, interferon (IFN-) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities. Furthermore, TRIM59 inhibited phosphorylation and dimerization of IRF3 and IRF7, suggesting that TRIM59 negatively regulates upstream kinases for IRFs. These findings indicate that TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways.3

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TRIM family proteins and their emerging roles in innate immunity

Cited by 897 publications

References 129 publications

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

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