scholarly journals IAP-Mediated Protein Ubiquitination in Regulating Cell Signaling

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1118 ◽  
Author(s):  
Baptiste Dumétier ◽  
Aymeric Zadoroznyj ◽  
Laurence Dubrez
Keyword(s):  
Signaling Pathways ◽  
Immune Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Protein Ubiquitination ◽  
Family Pattern ◽  
The Stability ◽  
Different Levels ◽  
Necrosis Factor ◽  
Stimulation Of

Over the last decade, the E3-ubiquitine ligases from IAP (Inhibitor of Apoptosis) family have emerged as potent regulators of immune response. In immune cells, they control signaling pathways driving differentiation and inflammation in response to stimulation of tumor necrosis factor receptor (TNFR) family, pattern-recognition receptors (PRRs), and some cytokine receptors. They are able to control the activity, the cellular fate, or the stability of actors of signaling pathways, acting at different levels from components of receptor-associated multiprotein complexes to signaling effectors and transcription factors, as well as cytoskeleton regulators. Much less is known about ubiquitination substrates involved in non-immune signaling pathways. This review aimed to present IAP ubiquitination substrates and the role of IAP-mediated ubiquitination in regulating signaling pathways.

scholarly journals TNFRSF14 deficiency protects against ovariectomy-induced adipose tissue inflammation

2014 ◽  
Vol 220 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Eun-Kyung Choi ◽  
Woon-Ki Kim ◽  
Ok-Joo Sul ◽  
Yun-Kyung Park ◽  
Eun-Sook Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Adipose Tissue ◽  
Tumor Necrosis ◽  
Ovarian Function ◽  
Tumor Necrosis Factor Receptor ◽  
Oxygen Species ◽  
Adipose Tissue Inflammation ◽  
Metabolic Perturbation ◽  
Necrosis Factor

To elucidate the role of tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in metabolic disturbance due to loss of ovarian function, ovariectomy (OVX) was performed in TNFRSF 14-knockout mice. OVX increased fat mass and infiltration of highly inflammatory CD11c cells in the adipose tissue (AT), which was analyzed by flow cytometry, and resulted in disturbance of glucose metabolism, whereas TNFRSF14 deficiency attenuated these effects. TNFRSF14 deficiency decreased recruitment of CD11c-expressing cells in AT and reduced the polarization of bone marrow-derived macrophages to M1. Upon engagement of LIGHT, a TNFRSF14 ligand, TNFRSF14 enhanced the expression of CD11c via generation of reactive oxygen species, suggesting a role of TNFRSF14 as a redox modulator. TNFRSF14 participated in OVX-induced AT inflammation via upregulation of CD11c, resulting in metabolic perturbation. TNFRSF14 could be used as a therapeutic target for the treatment of postmenopausal syndrome by reducing AT inflammation.

scholarly journals Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells

2015 ◽  
Vol 89 (23) ◽  
pp. 12118-12130 ◽  
Author(s):  
Ferdinand Roesch ◽  
Léa Richard ◽  
Réjane Rua ◽  
Françoise Porrot ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Proinflammatory Cytokine ◽  
Tumor Necrosis ◽  
Cellular Proteins ◽  
Accessory Protein ◽  
Infected Cells ◽  
Hiv 1 ◽  
Necrosis Factor ◽  
Stimulation Of

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.

The Role of the Tumor Necrosis Factor Receptor in 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis in Mice

2005 ◽  
Vol 50 (9) ◽  
pp. 1669-1676 ◽  
Author(s):  
Minoru Nakai ◽  
Kaori Sudo ◽  
Yasuhiro Yamada ◽  
Yasushi Kojima ◽  
Tomohiro Kato ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Sulfonic Acid ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
Necrosis Factor

scholarly journals Opposing role of tumor necrosis factor receptor 1 signaling in T cell-mediated hepatitis and bacterial infection in mice

Hepatology ◽  
2016 ◽  
Vol 64 (2) ◽  
pp. 508-521 ◽  
Author(s):  
Raluca Wroblewski ◽  
Marietta Armaka ◽  
Vangelis Kondylis ◽  
Manolis Pasparakis ◽  
Henning Walczak ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Bacterial Infection ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

scholarly journals Role of TNFR1 in the innate airway hyperresponsiveness of obese mice

2012 ◽  
Vol 113 (9) ◽  
pp. 1476-1485 ◽  
Author(s):  
Ming Zhu ◽  
Alison S. Williams ◽  
Lucas Chen ◽  
Allison P. Wurmbrand ◽  
Erin S. Williams ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Tumor Necrosis Factor Receptor ◽  
Lavage Fluid ◽  
Forced Oscillation Technique ◽  
Obese Mice ◽  
Wild Type ◽  
Necrosis Factor

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

scholarly journals Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

2016 ◽  
Vol Volume 11 ◽  
pp. 1705-1712 ◽  
Author(s):  
Masaki Fujita ◽  
Ouchi Hiroshi ◽  
Satoshi Ikemage ◽  
Eiji Harada ◽  
Takemasa Matsumoto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Pulmonary Emphysema ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

Is protein context responsible for peptide-mediated interactions?

2019 ◽  
Vol 15 (4) ◽  
pp. 280-295 ◽  
Author(s):  
Peng Zhou ◽  
Qingqing Miao ◽  
Fugang Yan ◽  
Zhongyan Li ◽  
Qianhu Jiang ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
The Stability ◽  
Cell Signaling Pathways

Many cell signaling pathways are orchestrated by the weak, transient, and reversible peptide-mediated interactions (PMIs). Here, the role of protein context in contributing to the stability and specificity of PMIs is investigated systematically.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

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