Prevention of Constitutive TNF Receptor 1 Signaling by Silencer of Death Domains

Jiang, Ying-Ping; Woronicz, John; Liu, Wei; Goeddel, David V.

doi:10.1126/science.283.5401.543

Cited by 371 publications

(301 citation statements)

References 17 publications

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“…Finally, it is possible that intracellular TNFR1 interacts with intracellular proteins different from those identified as interacting with plasma membrane receptor. One such candidate could be SODD (silencer of death domains), which has recently been reported to bind to the intracellular region of TNFR1 in the absence of TNF, thereby preventing receptor self-aggregation and blocking the recruitment of TRADD and down-stream signaling (Jiang et al, 1999). However, in preliminary experiments we did not see co-localization of SODD with TNFR1 in the Golgi (Gaeta ML, unpublished observation).…”

Section: Figurementioning

confidence: 79%

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

Gaeta

Johnson

Kluger

et al. 2000

Laboratory Investigation

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SUMMARY:TNF signals are mediated through two different receptors, TNFR1 and TNFR2. In endothelial cells, TNFR1 is predominantly localized in the Golgi apparatus and TNFR2 on the plasma membrane. To investigate structural features responsible for the disparate localization, endothelial cells were transfected with epitope-tagged or green fluorescent protein-fused wild type and mutant receptor molecules. Wild type receptors recapitulated the distribution of endogenous receptors. Deletions of the entire TNFR1 intracellular domain or of the C-terminal death domain (TNFR1 ϪDD ) allowed expression of the receptor on the plasma membrane. However, addition of the death domain to the C-terminus of TNFR2 (TNFR2 ϩDD ) did not lead to Golgi-retention of this chimeric receptor. Overexpressed TNFR1, TNFR2, and TNFR2 ϩDD increased basal expression of a cotransfected NF-B-dependent promotor-reporter gene. Overexpressed TNFR1 ϪDD did not activate NF-B but acted as a ligand-specific dominant negative inhibitor of TNF actions. Unexpectedly, TNF responses were also inhibited by overexpressed TNFR1 and TNFR2 ϩDD , but not TNFR2. We conclude that the death domain of TNFR1 is required for retention of TNFR1 in the Golgi apparatus but is not sufficient to direct Golgi retention of a TNFR2 ϩDD chimera, and that overexpressed receptors that contain the death domain (TNFR1 and TNFR2 ϩDD ) spontaneously activate NF-B while inhibiting TNF responses. (Lab Invest 2000, 80:1185-1194.

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Section: Figurementioning

confidence: 79%

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

Gaeta

Johnson

Kluger

et al. 2000

Laboratory Investigation

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“…41 It has been reported that Hsp70 associated with Bag-4 binds to the death domain of TNFR1 or DR3 and thus prevents self-aggregation to functional trimers initiating caspasedependent apoptotic cell death. 42 Therefore, we hypothesized that membrane-bound Hsp70/Bag-4 might also be linked to the cytosolic domain of TNFR1. However, neither CX þ /CXÀ nor Colo þ /ColoÀ carcinoma sublines exhibited TNFR1 or DR3 on their cell membranes.…”

Section: Discussionmentioning

confidence: 99%

Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells

et al. 2004

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CX þ /CXÀ and Colo þ /ColoÀ tumor sublines with stable heat shock protein 70 (Hsp70) high and low membrane expression were generated by fluorescence activated cell sorting of the parental human colon (CX2) and pancreas (Colo357) carcinoma cell lines, using an Hsp70-specific antibody. Two-parameter flow cytometry revealed that Hsp70 colocalizes with Bag-4, also termed silencer of death domain, not only in the cytosol but also on the plasma membrane. After nonlethal c-irradiation, the percentage of membranepositive cells and the protein density of Hsp70 and Bag-4 were found to be strongly upregulated in carcinoma sublines with initially low expression levels (CXÀ, ColoÀ). Membrane expression of Hsp70 was also elevated in Bag-4 overexpressing HeLa cervix carcinoma cells when compared to neo-transfected cells. In response to c-irradiation, neotransfected HeLa cells behaved like Hsp70/Bag-4 lowexpressing CXÀ and ColoÀ, and Bag-4-transfected HeLa cells like Hsp70/Bag-4 high-expressing carcinoma sublines CX þ and Colo þ . Immunoprecipitation studies further confirmed colocalization of Hsp70 and Bag-4 but also point to an association of Hsp70 and Hsp40 on the plasma membrane of CX þ and Colo þ cells; on CXÀ and ColoÀ tumor sublines, Hsp40 was detectable in the absence of Hsp70 and Bag-4. Other co-chaperones including Hsp60 and Hsp90 were neither found on the cell surface of CX þ /CXÀ, Colo þ /ColoÀ nor on HeLa neo-/HeLa Bag-4-transfected tumor cells. Functionally, Hsp70/Bag-4 and Hsp70/Hsp40 membrane-positive tumor cells appeared to be better protected against radiation-induced effects, including G2/M arrest and growth inhibition, on the one hand. On the other hand, membrane-bound Hsp70, but neither Bag-4 nor Hsp40, served as a recognition site for the cytolytic attack mediated by natural killer cells.

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“…This offers new insights into the biological functions of BMPs (Chen et al, 2001). There are proteins that associate with cytokine receptors, such as SODD (for silencer of death domain) (Jiang et al, 1999), sentris (Okura et al, 1996), and c-FLIP (Scaffidi et al, 1999). These can also negatively regulate apoptosis, again independently of NF-κB.…”

Section: Evidence That Apoptosis Is Unaffected By Nf-kappabmentioning

confidence: 99%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

206

168

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Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

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Prevention of Constitutive TNF Receptor 1 Signaling by Silencer of Death Domains

Cited by 371 publications

References 17 publications

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells

Nuclear Factor-κB Activation: A Question of Life or Death

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