Differential activation of nuclear factor‐κB by tumour necrosis factor receptor subtypes. TNFR1 predominates whereas TNFR2 activates transcription poorly

McFarlane, Shona Moira; Pashmi, Ghazaleh; Connell, Michelle; Littlejohn, Alison F; Tucker, Steven; Vandenabeele, Peter; MacEwan, David J.

doi:10.1016/s0014-5793(02)02450-x

Cited by 78 publications

(66 citation statements)

References 50 publications

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“…This study suggests that TNFR2 contributes with more than a "ligand passing" role, as also shown for NFκB activation in HeLa and HEK 293cells (McFarlane et al, 2002). Our study supports the view that TNFR2 independently can activate cellular responses and thus contributes with more than a ligand passing role, as also shown for NFκB activation of HeLa and HEK 293 cells (McFarlane et al, 2002) and for activation of the tyrosine kinase Etk/Bmx in angiogenesis (Pan et al, 2002).…”

Section: Discussionsupporting

confidence: 87%

Distinct Differences between TNF Receptor 1- and TNF Receptor 2- mediated Activation of NFκB

Thommesen¹,

Lægreid²

2005

BMB Reports

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Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors, TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and biological roles. In the present study, TNFR2 and TNFR1 signal transduction mechanisms involved in activation of NFκB and CMV promoter-enhancer were compared with respect to their susceptibility towards inhibitors of intracellular signaling. For this, we used SW480 cells, where we have shown that TNF-signaling can occur independently through each of the two receptors. The TNFR1 response was inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA), and by sodium salicylate, while TNFR2-mediated activation of NFκB and CMV promoter-enhancer was resistant to these compounds. The signaling mechanisms known to be affected by these inhibitors include phospholipases as well as redox-and pH-sensitive intracellular components. Our results imply that TNFR2 signaling involved in NFκB activation proceeds independently of these inhibitor-sensitive signaling components, indicating distinct signaling pathways not shared with TNFR1.

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Section: Discussionsupporting

confidence: 87%

Distinct Differences between TNF Receptor 1- and TNF Receptor 2- mediated Activation of NFκB

Thommesen¹,

Lægreid²

2005

BMB Reports

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“…TNF receptor complexes were isolated using a similar method to that used previously for TRAIL, and because HeLa cells do not express TNF-R2, TNF-R1 complexes could be studied exclusively (66). Treatment of cells with TNF led to immediate recruitment of TRADD, TRAF2, and RIP to the TNF precipitates (Fig.…”

Section: Pma-mediated Pkc Activation Alsomentioning

confidence: 99%

Protein Kinase C Modulates Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis by Targeting the Apical Events of Death Receptor Signaling

Harper

Hughes

Farrow

et al. 2003

Journal of Biological Chemistry

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We have further examined the mechanism by which phorbol ester-mediated protein kinase C (PKC) activation protects against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. We now report that activation of PKC targets death receptor signaling complex formation. Pre-treatment with 12-Otetradecanoylphorbol-13-acetate (PMA) led to inhibition of TRAIL-induced apoptosis in HeLa cells, which was characterized by a reduction in phosphatidylserine (PS) externalization, decreased caspase-8 processing, and incomplete maturation and activation of caspase-3. These effects of PMA were completely abrogated by the PKC inhibitor, bisindolylmaleimide I (Bis I), clearly implicating PKC in the protective effect of PMA. TRAIL-induced mitochondrial release of the apoptosis mediators cytochrome c and Smac was blocked by PMA. This, together with the observed decrease in Bid cleavage, suggested that PKC activation modulates apical events in TRAIL signaling upstream of mitochondria. This was confirmed by analysis of TRAIL death-inducing signaling complex formation, which was disrupted in PMA-treated cells as evidenced by a marked reduction in Fas-associated death domain protein (FADD) recruitment, an effect that could not be explained by any change in FADD phosphorylation state. In an in vitro binding assay, the intracellular domains of both TRAIL-R1 and TRAIL-R2 bound FADD: activation of PKC significantly inhibited this interaction suggesting that PKC may be targeting key apical components of death receptor signaling. Significantly, this effect was not confined to TRAIL, because isolation of the native TNF receptor signaling complex revealed that PKC activation also inhibited TNF receptor-associated death domain protein recruitment to TNF-R1 and TNF-induced phosphorylation of I B-␣. Taken together, these results show that PKC activation specifically inhibits the recruitment of key obligatory death domain-containing adaptor proteins to their respective membrane-associated signaling complexes, thereby modulating TRAIL-induced apoptosis and TNF-induced NF-B activation, respectively.Death receptors belong to a subgroup of the tumor necrosis factor (TNF) 1 receptor/nerve growth factor superfamily. Members of this subfamily are characterized by a number of conserved cysteine-rich repeats within the extracellular domain and the presence of a "death domain" (DD) motif within the intracellular domain. The DD was first identified in the intracellular domain of TNF receptor-1 (TNF-R1) and was described as a region of ϳ80 amino acids containing a number of key residues that appeared to be critical for TNF-mediated cytotoxicity. These residues also appear to be highly conserved within other members of the death receptor subfamily (1).TNF-related apoptosis-inducing ligand (TRAIL) was identified because of its high sequence homology to other TNF family members (2, 3). The TRAIL receptor family is unusually complex in that it consists of at least four membrane-bound members. TRAIL-R1 (DR4) and -R2 (DR5, Killer,...

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“…TNFR1-specific muteins, but not TNFR2-specific muteins have also been shown to induce NF-kB activation. 38,39 Whereas both soluble and membrane-bound TNF have comparable bioactivities when acting on TNFR1, membrane-bound TNF is the prime activating ligand for TNFR2. 40 The membrane-bound form of TNF can also trigger effective cytotoxicity by stimulating TNFR2.…”

Section: Tnf Life/death Switching In Other Human Leukaemia Cellsmentioning

confidence: 99%

Granulocyte macrophage-colony stimulating factor and interleukin-3 increase expression of type II tumour necrosis factor receptor, increasing susceptibility to tumour necrosis factor-induced apoptosis. Control of leukaemia cell life/death switching

Rae

MacEwan

2004

Cell Death Differ

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Tumour necrosis factor (TNF) induces apoptosis in a range of cell types via its two receptors, TNFR1 and TNFR2. Here, we demonstrate that proliferation and TNFR2 expression was increased in human leukaemic TF-1 cells by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), with TNFR1 expression unaffected. Consequently, they switch from a proliferative to a TNF-induced apoptotic phenotype. Raised TNFR2 expression and susceptibility to TNF-induced apoptosis was not a general effect of proliferation as IL-1b and IFN-c both proliferated TF-1 cells with no effect on TNFR expression or apoptosis. Although raised TNFR2 expression correlated with the apoptotic phenotype, stimulation of apoptosis in GM-CSF-pretreated cells was mediated by TNFR1, with stimulation of TNFR2 alone insufficient to initiate cell death. However, TNFR2 did play a role in apoptotic and proliferative responses as they were blocked by the presence of an antagonistic TNFR2 antibody. Additionally, coincubation with cycloheximide blocked the mitotic effects of GM-CSF or IL-3, allowing only the apoptotic responses of TNF to persist. TNF life/death was also observed in K562, but not MOLT-4 and HL-60 human leukaemic cell types. These findings show a cooperative role of TNFR2 in the TNF life/death switching phenomenon.

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Differential activation of nuclear factor‐κB by tumour necrosis factor receptor subtypes. TNFR1 predominates whereas TNFR2 activates transcription poorly

Cited by 78 publications

References 50 publications

Distinct Differences between TNF Receptor 1- and TNF Receptor 2- mediated Activation of NFκB

Distinct Differences between TNF Receptor 1- and TNF Receptor 2- mediated Activation of NFκB

Protein Kinase C Modulates Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis by Targeting the Apical Events of Death Receptor Signaling

Granulocyte macrophage-colony stimulating factor and interleukin-3 increase expression of type II tumour necrosis factor receptor, increasing susceptibility to tumour necrosis factor-induced apoptosis. Control of leukaemia cell life/death switching

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