scholarly journals TRUSS, a Novel Tumor Necrosis Factor Receptor 1 Scaffolding Protein That Mediates Activation of the Transcription Factor NF-κB

2003 ◽  
Vol 23 (22) ◽  
pp. 8334-8344 ◽  
Author(s):  
Surinder M. Soond ◽  
Jennifer L. Terry ◽  
Jeff D. Colbert ◽  
David W. H. Riches
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Proximal Region ◽  
Scaffolding Protein ◽  
Death Domain ◽  
Interacting Protein ◽  
Mouse Tissues ◽  
Tnf Α ◽  
Necrosis Factor

ABSTRACT We describe the cloning and characterization of tumor necrosis factor receptor (TNF-R)-associated ubiquitous scaffolding and signaling protein (TRUSS), a novel TNF-R1-interacting protein of 90.7 kDa. TRUSS mRNA was ubiquitously expressed in mouse tissues but was enriched in heart, liver, and testis. Coimmunoprecipitation experiments showed that TRUSS was constitutively associated with unligated TNF-R1 and that the complex was relatively insensitive to stimulation with TNF-α. Deletion mutagenesis of TNF-R1 indicated that TRUSS interacts with both the membrane-proximal region and the death domain of TNF-R1. In addition, the N-terminal region of TRUSS (residues 1 to 440) contains sequences that permit association with the cytoplasmic domain of TNF-R1. Transient overexpression of TRUSS activated NF-κB and increased NF-κB activation in response to ligation of TNF-R1. In contrast, a COOH-terminal-deletion mutant of TRUSS (TRUSS1-723) was found to inhibit NF-κB activation by TNF-α. Coprecipitation and coimmunoprecipitation assays revealed that TRUSS can interact with TRADD, TRAF2, and components of the IKK complex. These findings suggest that TRUSS may serve as a scaffolding protein that interacts with TNF-R1 signaling proteins and may link TNF-R1 to the activation of IKK.

scholarly journals Restoration of NF-κB Activation by Tumor Necrosis Factor Alpha Receptor Complex-Targeted MEKK3 in Receptor-Interacting Protein-Deficient Cells

2004 ◽  
Vol 24 (24) ◽  
pp. 10757-10765 ◽  
Author(s):  
Marzenna Blonska ◽  
Yun You ◽  
Romas Geleziunas ◽  
Xin Lin
Keyword(s):  
Tumor Necrosis Factor ◽  
Fusion Protein ◽  
Tumor Necrosis ◽  
Receptor Complex ◽  
Death Domain ◽  
Necrosis Factor Alpha ◽  
Interacting Protein ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Receptor-interacting protein (RIP) plays a critical role in tumor necrosis factor alpha (TNF-α)-induced NF-κB activation. However, the mechanism by which RIP mediates TNF-α-induced signal transduction is not fully understood. In this study, we reconstituted RIP-deficient Jurkat T cells with a fusion protein composed of full-length MEKK3 and the death domain of RIP (MEKK3-DD). In these cells, MEKK3-DD substitutes for RIP and directly associates with TRADD in TNF receptor complexes following TNF-α stimulation. We found that TNF-α-induced NF-κB activation was fully restored by MEKK3-DD in these cells. In contrast, expression of a fusion protein composed of NEMO, a component of the IκB kinase complex, and the death domain of RIP (NEMO-DD) cannot restore TNF-α-induced NF-κB activation in RIP-deficient cells. These results indicate that the role of RIP is to specifically recruit MEKK3 to the TNF-α receptor complex, whereas the forced recruitment of NEMO to the TNF-α receptor complex is insufficient for TNF-α-induced NF-κB activation. Although MEKK2 has a high degree of homology with MEKK3, MEKK2-DD, unlike MEKK3-DD, also fails to restore TNF-α-induced NF-κB activation in RIP-deficient cells, indicating that RIP-dependent recruitment of MEKK3 plays a specific role in TNF-α signaling.

scholarly journals The Epstein-Barr Virus Oncoprotein Latent Membrane Protein 1 Engages the Tumor Necrosis Factor Receptor-Associated Proteins TRADD and Receptor-Interacting Protein (RIP) but Does Not Induce Apoptosis or Require RIP for NF-κB Activation

1999 ◽  
Vol 19 (8) ◽  
pp. 5759-5767 ◽  
Author(s):  
Kenneth M. Izumi ◽  
Ellen Cahir McFarland ◽  
Adrian T. Ting ◽  
Elisabeth A. Riley ◽  
Brian Seed ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Tumor Necrosis Factor Receptor ◽  
Death Domain ◽  
Interacting Protein ◽  
Barr Virus ◽  
Epstein Barr ◽  
Necrosis Factor

ABSTRACT A site in the Epstein-Barr virus (EBV) transforming protein LMP1 that constitutively associates with the tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein TRADD to mediate NF-κB and c-Jun N-terminal kinase activation is critical for long-term lymphoblastoid cell proliferation. We now find that LMP1 signaling through TRADD differs from TNFR1 signaling through TRADD. LMP1 needs only 11 amino acids to activate NF-κB or synergize with TRADD in NF-κB activation, while TNFR1 requires ∼70 residues. Further, LMP1 does not require TRADD residues 294 to 312 for NF-κB activation, while TNFR1 requires TRADD residues 296 to 302. LMP1 is partially blocked for NF-κB activation by a TRADD mutant consisting of residues 122 to 293. Unlike TNFR1, LMP1 can interact directly with receptor-interacting protein (RIP) and stably associates with RIP in EBV-transformed lymphoblastoid cell lines. Surprisingly, LMP1 does not require RIP for NF-κB activation. Despite constitutive association with TRADD or RIP, LMP1 does not induce apoptosis in EBV-negative Burkitt lymphoma or human embryonic kidney 293 cells. These results add a different perspective to the molecular interactions through which LMP1, TRADD, and RIP participate in B-lymphocyte activation and growth.

IL-1β and TNF-α Regulate IL-6-type Cytokines in Gingival Fibroblasts

2008 ◽  
Vol 87 (6) ◽  
pp. 558-563 ◽  
Author(s):  
P. Palmqvist ◽  
P. Lundberg ◽  
I. Lundgren ◽  
L. Hänström ◽  
U.H. Lerner
Keyword(s):  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Tumor Necrosis ◽  
Map Kinases ◽  
Tumor Necrosis Factor Receptor ◽  
Oncostatin M ◽  
Gingival Fibroblasts ◽  
Tnf Α ◽  
Necrosis Factor

Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1β and tumor necrosis factor-α (TNF-α) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1β and TNF-α. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1β. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-κB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases. Abbreviations: IL-1α (interleukin-1α); IL-1β (interleukin-1β); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); α(1)-coll. I (α(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); α-MEM (α modification of Minimum Essential Medium); and FCS (fetal calf serum).

scholarly journals Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Trine B. Levring ◽  
Martin Kongsbak-Wismann ◽  
Anna K. O. Rode ◽  
Fatima A. H. Al-Jaberi ◽  
Daniel V. Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Glucose Uptake ◽  
Tumor Necrosis ◽  
Gradient Centrifugation ◽  
Tumor Necrosis Factor Receptor ◽  
Down Regulation ◽  
Interacting Protein ◽  
Human T Cells ◽  
Necrosis Factor

Abstract In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement

2007 ◽  
Vol 86 (11) ◽  
pp. 1089-1094 ◽  
Author(s):  
I. Andrade ◽  
T.A. Silva ◽  
G.A.B. Silva ◽  
A.L. Teixeira ◽  
M.M. Teixeira
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tooth Movement ◽  
Tumor Necrosis Factor Receptor ◽  
Orthodontic Tooth Movement ◽  
Receptor Type ◽  
Periodontal Tissues ◽  
Tnf Α ◽  
Necrosis Factor

Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-α plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55−/−). Levels of TNF-α and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-α was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55−/− mice at this time-point. The number of TRAP-positive osteoclasts in p55−/− mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55−/− mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels.

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