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https://www.readbyqxmd.com/read/28807517/trim21-and-the-function-of-antibodies-inside-cells
#1
REVIEW
David A Rhodes, David A Isenberg
Therapeutic antibodies targeting disease-associated antigens are key tools in the treatment of cancer and autoimmunity. So far, therapeutic antibodies have targeted antigens that are, or are presumed to be, extracellular. A largely overlooked property of antibodies is their functional activity inside cells. The diverse literature dealing with intracellular antibodies emerged historically from studies of the properties of some autoantibodies. The identification of tripartite motif (TRIM) 21 as an intracellular Fc receptor linking cytosolic antibody recognition to the ubiquitin proteasome system brings this research into sharper focus...
August 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28753623/solution-nmr-structure-of-the-trim21-b-box2-and-identification-of-residues-involved-in-its-interaction-with-the-ring-domain
#2
Amélie Wallenhammar, Madhanagopal Anandapadamanaban, Alexander Lemak, Claudio Mirabello, Patrik Lundström, Björn Wallner, Maria Sunnerhagen
Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein ligase implicated in innate immune signaling by acting as an autoantigen and by modifying interferon regulatory factors. Here we report the three-dimensional solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21 residues 86-130, consists of a short α-helical segment with an N-terminal short β-strand and two anti-parallel β-strands jointly found the core, and adopts a RING-like fold...
2017: PloS One
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#3
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711442/association-of-ev71-3c-polymorphisms-with-clinical-severity
#4
Hsuan-Yin Ma, Chun-Yi Lu, Kuo-Chien Tsao, Hsiu-Ming Shih, Ai-Ling Cheng, Li-Min Huang, Luan-Yin Chang
OBJECTIVES: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity. METHODS: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed...
June 28, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28701773/trim21-is-critical-for-survival-of-toxoplasma-gondii-infection-and-localises-to-gbp-positive-parasite-vacuoles
#5
Clémence Foltz, Anna Napolitano, Rabia Khan, Barbara Clough, Elizabeth M Hirst, Eva-Maria Frickel
Interferon gamma (IFNγ) is the major proinflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing the destruction of the parasitophorous vacuole (PV). We previously identified TRIM21 as an IFNγ-driven E3 ubiquitin ligase mediating the deposition of ubiquitin around pathogen inclusions. Here, we show that TRIM21 knockout mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of serum inflammatory cytokines and higher parasite burden in the peritoneum and brain...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592884/enhancement-of-th1-th17-inflammation-by-trim21-in-beh%C3%A3-et-s-disease
#6
Yuri Ahn, Ji-Hye Hwang, Zhenlong Zheng, Dongsik Bang, Do-Young Kim
The etiology of Behçet's disease (BD), a chronic, multisystemic autoinflammatory and autoimmune disease, remains unknown; however, researchers have postulated that infectious agents, such as herpes simplex virus, are significant triggering factors of BD. Tripartite motif-containing (TRIM) proteins exhibit antiviral properties, mediating antiviral defense mechanisms. The purpose of this study was to investigate TRIM21 protein expression in the monocytes of BD patients and to identify the role of TRIM21 in immune dysregulation in BD...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576352/reprint-of-alterations-of-trim21-mrna-expression-during-monocyte-maturation
#7
Marzena Lenart, Magdalena Rutkowska-Zapała, Rafał Szatanek, Kazimierz Węglarczyk, Małgorzata Stec, Karolina Bukowska-Strakova, Anna Gruca, Jarosław Czyż, Maciej Siedlar
Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16(+) monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and non-classical (CD14(+)CD16(++)) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages...
June 2017: Immunobiology
https://www.readbyqxmd.com/read/28417151/a-review-of-the-role-and%C3%A2-clinical-utility-of-anti-ro52-trim21-in-systemic-autoimmunity
#8
REVIEW
Adrian Y S Lee
Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found in a number of systemic autoimmune conditions including Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis, appearing in about half of these patients. Once coupled with its closely related antibody, anti-Ro60 as the anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct pathogenic disease involvement and distinct clinical properties. As a result, recent attention has turned to this antibody and its clinical associations and utility...
August 2017: Rheumatology International
https://www.readbyqxmd.com/read/28211536/expression-profiling-of-trim-protein-family-in-thp1-derived-macrophages-following-tlr-stimulation
#9
Mei-Xiu Jiang, Xuan Hong, Bin-Bin Liao, Shui-Zhen Shi, Xiao-Fang Lai, Huai-Yu Zheng, Lin Xie, Yuan Wang, Xiao-Lei Wang, Hong-Bo Xin, Mingui Fu, Ke-Yu Deng
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119462/harnessing-innate-immunity-to-fight-neurodegeneration
#10
Alexandra A Mushegian
TRIM21 prevents antibody-bound tau proteins from aggregating in cells.
January 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049840/cytosolic-fc-receptor-trim21-inhibits-seeded-tau-aggregation
#11
William A McEwan, Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L Oblak, Bernardino Ghetti, Michel Goedert, Leo C James
Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27943421/trim21-is-important-in-the-early-phase-of-inflammation-in-the-imiquimod-induced-psoriasis-like-skin-inflammation-mouse-model
#12
Hanne Vinter, Ane Langkilde, Vijole Ottosson, Alexander Espinosa, Marie Wahren-Herlenius, Line Raaby, Claus Johansen, Lars Iversen
Tripartite motif-containing protein 21 (TRIM21) regulates pro-inflammatory cytokines and type I interferons and acts as an autoantigen in certain autoimmune diseases, but TRIM21 has not been investigated in psoriasis. It has been suggested that TRIM21 may have a dual function; in the early phase of inflammation, it may function as a stimulator; but upon immune stimulation, its ubiquitinating mode of action may shift from stabilization to degradation of IRF3 causing inhibition of the immune responses. The imiquimod (IMQ)-induced psoriasis-like mouse model displays features similar to those of human psoriasis...
August 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/27936488/ro52-trim21-deficient-expression-and-function-in-different-subsets-of-peripheral-blood-mononuclear-cells-is-associated-with-a-proinflammatory-cytokine-response-in-patients-with-idiopathic-inflammatory-myopathies
#13
D Gómez-Martín, A S Galindo-Feria, A Barrera-Vargas, J Merayo-Chalico, G Juárez-Vega, J Torres-Ruiz, J Alcocer-Varela
The presence of anti-Ro52/tripartite motif 21 (Trim21) autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyse Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with proinflammatory cytokine production. We included 18 patients with recent-onset IIM and 18 age- and gender-matched healthy donors...
April 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27888685/label-free-piezoelectric-biosensor-for-prognosis-and-diagnosis-of-systemic-lupus-erythematosus
#14
Noelle M do Nascimento, Augusto Juste-Dolz, Elena Grau-García, Jose A Román-Ivorra, Rosa Puchades, Angel Maquieira, Sergi Morais, David Gimenez-Romero
An autoantigen piezoelectric sensor to quantify specific circulating autoantibodies in human serum is developed. The sensor consisted on a quartz crystal microbalance with dissipation monitoring (QCM-D) where TRIM21 and TROVE2 autoantigens were covalently immobilized, allowing the selective determination of autoantibodies for diagnosis and prognosis of Systemic Lupus Erythematosus (SLE). The sensitivity of the biosensor, measured as IC50 value, was 1.51U/mL and 0.32U/mL, for anti-TRIM21 and anti-TROVE2 circulating autoantibodies, respectively...
April 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27881870/antibody-antigen-kinetics-constrain-intracellular-humoral-immunity
#15
Maria Bottermann, Heidrun Elisabeth Lode, Ruth E Watkinson, Stian Foss, Inger Sandlie, Jan Terje Andersen, Leo C James
During infection with non-enveloped viruses, antibodies stimulate immunity from inside cells by activating the cytosolic Fc receptor TRIM21. This intracellular humoral response relies on opsonized viral particles reaching the cytosol intact but the antigenic and kinetic constraints involved are unknown. We have solved the structure of a potent TRIM21-dependent neutralizing antibody in complex with human adenovirus 5 hexon and show how these properties influence immune activity. Structure-guided mutagenesis was used to generate antibodies with 20,000-fold variation in affinity, on-rates that differ by ~50-fold and off-rates by >175-fold...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27830973/trim21-is-a-novel-regulator-of-par-4-in-colon-and-pancreatic-cancer-cells
#16
Jeffrey Q Nguyen, Rosalyn B Irby
The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain...
January 2, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27773663/alterations-of-trim21-mrna-expression-during-monocyte-maturation
#17
Marzena Lenart, Magdalena Rutkowska-Zapała, Rafał Szatanek, Kazimierz Węglarczyk, Małgorzata Stec, Karolina Bukowska-Strakova, Anna Gruca, Jarosław Czyż, Maciej Siedlar
Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16(+) monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and non-classical (CD14(+)CD16(++)) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages...
October 18, 2016: Immunobiology
https://www.readbyqxmd.com/read/27758890/destabilization-of-fatty-acid-synthase-by-acetylation-inhibits-de-novo-lipogenesis-and-tumor-cell-growth
#18
Huai-Peng Lin, Zhou-Li Cheng, Ruo-Yu He, Lei Song, Meng-Xin Tian, Li-Sha Zhou, Beezly S Groh, Wei-Ren Liu, Min-Biao Ji, Chen Ding, Ying-Hong Shi, Kun-Liang Guan, Dan Ye, Yue Xiong
Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacologic inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity, and other diseases. Here, we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin ligase TRIM21...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27706114/antibodies-against-antigens-related-to-scleroderma-in-a-cohort-of-patients-with-morphea
#19
Mariachiara Arisi, Ilaria Cavazzana, Maria E Cerutti, Fabio Ferrari, Nice Carabellese, Maria T Rossi, Angela Tincani, Pier G Calzavara-Pinton, Franco Franceschini
BACKGROUND: Morphea is a rare fibrosing skin disorder. Antinuclear antibodies (ANA), antihistone and rheumatoid factor are detected in high rate of morphea cases. Scleroderma-related antibodies are usually absent. METHODS: 21 adult patients affected by morphea were examined at the time of enrollment and after 6 months with the assessment of clinical outcome measures of disease severity and damage. Healthy subjects were considered as normal controls while patients affected by systemic sclerosis and other connective tissue diseases (CTD) were considered as pathological controls...
October 5, 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27502187/the-emerging-roles-of-the-ddx41-protein-in-immunity-and-diseases
#20
REVIEW
Yan Jiang, Yanping Zhu, Zhi-Jie Liu, Songying Ouyang
RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box helicases comprise the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recent literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41...
February 2017: Protein & Cell
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