scholarly journals A Regulatory Role for TRAF1 in Antigen-induced Apoptosis of  T Cells

1997 ◽  
Vol 185 (10) ◽  
pp. 1777-1783 ◽  
Author(s):  
Daniel E. Speiser ◽  
Soo Young Lee ◽  
Brian Wong ◽  
Joseph Arron ◽  
Angela Santana ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Cytokine Production ◽  
Biological Effects ◽  
Tumor Necrosis Factor Receptor ◽  
Tnf Receptor ◽  
Cell Type ◽  
Signaling Complex ◽  
Induced Apoptosis ◽  
Necrosis Factor

Tumor necrosis factor receptor (TNFR)–associated factor 2 (TRAF2) and TRAF1 were found as components of the TNFR2 signaling complex, which exerts multiple biological effects on cells such as cell proliferation, cytokine production, and cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-κB, but the role of TRAF1 has not been previously determined. Here we show in transgenic mice that TRAF1 overexpression inhibits antigen-induced apoptosis of CD8+ T lymphocytes. Our results demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and also support the hypothesis that the combination of TRAF proteins in a given cell type determines distinct biological effects triggered by members of the TNF receptor superfamily.

scholarly journals UXT-V1 protects cells against TNF-induced apoptosis through modulating complex II formation

2011 ◽  
Vol 22 (8) ◽  
pp. 1389-1397 ◽  
Author(s):  
Yuefeng Huang ◽  
Liang Chen ◽  
Yi Zhou ◽  
Heng Liu ◽  
Jueqing Yang ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Complex ◽  
Tnf Receptor ◽  
Death Domain ◽  
Complex Ii ◽  
Signaling Complex ◽  
Induced Apoptosis ◽  
Necrosis Factor

Proteins that directly regulate tumor necrosis factor (TNF) signaling have critical roles in determining cell death and survival. Previously we characterized ubiquitously expressed transcript (UXT)-V2 as a novel transcriptional cofactor to regulate nuclear factor-κB in the nucleus. Here we report that another splicing isoform of UXT, UXT-V1, localizes in cytoplasm and regulates TNF-induced apoptosis. UXT-V1 knockdown cells are hypersensitive to TNF-induced apoptosis. We demonstrated that UXT-V1 is a new component of TNF receptor signaling complex. We found that UXT-V1 binds to TNF receptor-associated factor 2 and prevents TNF receptor–associated death domain protein from recruiting Fas-associated protein with death domain. More importantly, UXT-V1 is a short-half-life protein, the degradation of which facilitates the formation of the apoptotic receptor complex II in response to TNF treatment. This study demonstrates that UXT-V1 is a novel regulator of TNF-induced apoptosis and sheds new light on the underlying molecular mechanism of this process.

scholarly journals Apparently Normal Tumor Necrosis Factor Receptor 1 Signaling in the Absence of the Silencer of Death Domains

2003 ◽  
Vol 23 (18) ◽  
pp. 6609-6617 ◽  
Author(s):  
Robert Endres ◽  
Georg Häcker ◽  
Inge Brosch ◽  
Klaus Pfeffer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Death Receptor ◽  
High Dose ◽  
Wild Type ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT The silencer of death domains (SODD) has been proposed to prevent constitutive signaling of tumor necrosis factor receptor 1 (TNFR1) in the absence of ligand. Besides TNFR1, death receptor 3 (DR3), Hsp70/Hsc70, and Bcl-2 have been characterized as binding partners of SODD. In order to investigate the in vivo role of SODD, we generated mice congenitally deficient in expression of the sodd gene. No spontaneous inflammatory infiltrations were observed in any organ of these mice. Consistent with this finding, in the absence of SODD no alteration in the activation patterns of nuclear factor κB (NF-κB), stress kinases, or ERK1 or -2 was observed after stimulation with tumor necrosis factor (TNF). Activation of NF-κB by DR3 was also unchanged. The extents of DR3- and TNF-induced apoptosis were comparable in gene-deficient and wild-type cells. Protection of cells against heat shock as mediated by the Hsp70 system and against staurosporine-induced apoptosis was independent of SODD. Furthermore, resistance to high-dose lipopolysaccharide (LPS) injections, LPS-d-GalN injections, and infection with listeriae was similar in wild-type and gene-deficient mice. In conclusion, our data do not support the concept of a unique, nonredundant role of SODD for the functions of TNFR1, Hsp70, and DR3.

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.

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