Histamine Antagonizes Tumor Necrosis Factor (TNF) Signaling by Stimulating TNF Receptor Shedding from the Cell Surface and Golgi Storage Pool

ABSTRACT Viral infections often trigger host defensive reactions by activating intrinsic (intracellular) and extrinsic (receptor-mediated) apoptotic pathways. Poliovirus is known to encode an antiapoptotic function(s) suppressing the intrinsic pathway. Here, the effect of poliovirus nonstructural proteins on cell sensitivity to tumor necrosis factor (TNF)-induced (i.e., receptor-mediated) apoptosis was studied. This sensitivity is dramatically enhanced by the viral proteinase 2A, due, most likely, to inhibition of cellular translation. On the other hand, cells expressing poliovirus noncapsid proteins 3A and 2B exhibit strong TNF resistance. Expression of 3A neutralizes the proapoptotic activity of 2A and results in a specific suppression of TNF signaling, including the lack of activation of NF-κB, due to elimination of the TNF receptor from the cell surface. In agreement with this, poliovirus infection results in a dramatic decrease in TNF receptor abundance on the surfaces of infected cells as early as 4 h postinfection. Poliovirus proteins that confer resistance to TNF interfere with endoplasmic reticulum-Golgi protein trafficking, and their effect on TNF signaling can be imitated by brefeldin A, suggesting that the mechanism of poliovirus-mediated resistance to TNF is a result of aberrant TNF receptor trafficking.

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The Latency-Associated UL138 Gene Product of Human Cytomegalovirus Sensitizes Cells to Tumor Necrosis Factor Alpha (TNF- ) Signaling by Upregulating TNF- Receptor 1 Cell Surface Expression

Journal of Virology ◽

10.1128/jvi.05028-11 ◽

2011 ◽

Vol 85 (21) ◽

pp. 11409-11421 ◽

Cited By ~ 49

Author(s):

C. Montag ◽

J. A. Wagner ◽

I. Gruska ◽

B. Vetter ◽

L. Wiebusch ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Cell Surface ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Surface Expression ◽

Cell Surface Expression ◽

Tnf Receptor ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

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Faculty Opinions recommendation of Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020548.232661 ◽

2004 ◽

Author(s):

David Chaplin

Keyword(s):

Tumor Necrosis Factor ◽

Immune Activation ◽

Tumor Necrosis ◽

Inflammatory Diseases ◽

Innate Immune ◽

Tnf Receptor ◽

Innate Immune Activation ◽

Receptor Shedding ◽

Necrosis Factor

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Effect of serine protease inhibitors on the expression of cell surface and soluble forms of two types of tumor necrosis factor receptors

Immunology Letters ◽

10.1016/s0165-2478(97)87943-6 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 276

Author(s):

E Pócsik

Keyword(s):

Tumor Necrosis Factor ◽

Cell Surface ◽

Serine Protease ◽

Protease Inhibitors ◽

Tumor Necrosis ◽

Serine Protease Inhibitors ◽

Tumor Necrosis Factor Receptors ◽

Necrosis Factor

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The α and β Subunits of IκB Kinase (IKK) Mediate TRAF2-Dependent IKK Recruitment to Tumor Necrosis Factor (TNF) Receptor 1 in Response to TNF

Molecular and Cellular Biology ◽

10.1128/mcb.21.12.3986-3994.2001 ◽

2001 ◽

Vol 21 (12) ◽

pp. 3986-3994 ◽

Cited By ~ 100

Author(s):

Anne Devin ◽

Yong Lin ◽

Shoji Yamaoka ◽

Zhiwei Li ◽

Michael Karin ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Leucine Zipper ◽

Nuclear Translocation ◽

Ring Finger ◽

Tnf Receptor ◽

Death Domain ◽

Iκb Kinase ◽

Cytokine Tumor Necrosis Factor ◽

Necrosis Factor

ABSTRACT The activation of IκB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-κB. IKK is a complex composed of three subunits: IKKα, IKKβ, and IKKγ (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKKα and IKKβ catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKKα, IKKβ, and the RING finger domain of TRAF2, and either IKKα or IKKβ alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKKγ is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKKγ-deficient cells. Using TRAF2−/− cells, we demonstrated that the TNF-induced interaction between IKKγ and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2.

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Membrane lymphotoxin-α2β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist

Cell Death and Disease ◽

10.1038/s41419-021-03633-8 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Kirstin Kucka ◽

Isabell Lang ◽

Tengyu Zhang ◽

Daniela Siegmund ◽

Juliane Medler ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Asymmetric Structure ◽

Tnf Receptor ◽

Membrane Bound ◽

Necrosis Factor

AbstractIn the early 1990s, it has been described that LTα and LTβ form LTα2β and LTαβ2 heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ2–LTβR system has been intensively studied while the LTα2β–TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα2β–TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα2β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα2β (memLTα2β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα2β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.

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