Unraveling Function in the TNF Ligand and Receptor Families

Beutler, Bruce; Huffel, Christophe Van

doi:10.1126/science.8171316

Cited by 393 publications

(213 citation statements)

References 28 publications

Supporting

Mentioning

206

Contrasting

Order By: Relevance

“…Among the TNF-related cytokines, five ligands bind to death receptors, such as CD95L, TNF, lymphotoxin-␣ (LT␣), TRAIL and TWEAK, which was recently identified as a ligand for DR3/TRAMP. [44][45][46] As suggested by structural and biochemical data, all active ligands consist of three identical subunits and activate their receptors by oligomerization. 14,47 Another common feature is that, with the exception of LT␣, all are type II transmembrane proteins.…”

Section: Structure and Function Of Death Receptorsmentioning

confidence: 99%

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

et al. 2001

View full text Add to dashboard Cite

Section: Structure and Function Of Death Receptorsmentioning

confidence: 99%

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

et al. 2001

View full text Add to dashboard Cite

“…TNFR1 and TNFR2 are members of the TNF receptor superfamily characterized by cysteine-rich pseudorepeats in their extracellular regions (Beutler and van Huffel, 1994;Smith et al, 1994). Activation of TNFR1 appears to be sufficient to induce most common TNF reponses like activation of NFκB, cytotoxicity and proliferation (Tartaglia et al, 1991;Schutze et al, 1992;Laegreid et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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

Thommesen¹,

Lægreid²

2005

BMB Reports

View full text Add to dashboard Cite

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.

show abstract

“…Fhe 55 kDa TNF-receptor and Fas/APO-1 (CD95) belong to a family of surface receptors that also include the NGF receptor, CD40, CD27, 4-1BB and OX40 [1]. While most receptors of this family are implicated in proliferative processes, TNF receptor and Fas, when cross-linked by antibodies or their physiological ligands (TNF or the Fas ligand, respectively), frequently induce apoptosis [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

mtDNA‐depleted U937 cells are sensitive to TNF and Fas‐mediated cytototxicity

et al. 1995

View full text Add to dashboard Cite

It has been proposed that TNF cytotoxicity is mediated by reactive oxygen intermediates generated by uncoupling of mitochondrial respiration. We have compared sensitive U937 cells and derived cell lines depleted of mtDNA for their ability to undergo TNF-and Fas-induced apoptosis. Cells lacking around 98% of mtDNA were still sensitive to TNF-induced apoptosis. U937 cells devoid of mtDNA (U937-p °) were resistant to TNF, but this was due to the loss of its 55 kDa receptor. U937-p ° cells were also resistant to docosahexaenoic acid, which causes U937 cell death by lipid peroxidation. These cells were sensitive to anti-Fas toxicity. The results indicate that TNF and Fasinduced toxicity occurs by a mechanism mostly independent of mitochondrial free radical generation.The mechanism by which Fas ligation triggers apoptosis, as well as a general biochemical mechanism for the apoptosis process itself, are unknown [5]. Some reports have suggested, however, the lack of implication of oxidative damage in cytotoxicity induced with anti-Fas, using antioxidants [14,15] or anaerobic conditions [16].In the present work, we have studied the effect of TNF and anti-Fas on U937 cells and in derived cell lines depleted of mtDNA by prolonged exposure to low doses of ethidium bromide. Results indicate that impairment of mitochondrial function and lipid peroxidation do not play a key role in the apoptosis induced by both molecules in human myeloid cells.

show abstract

Unraveling Function in the TNF Ligand and Receptor Families

Cited by 393 publications

References 28 publications

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

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

mtDNA‐depleted U937 cells are sensitive to TNF and Fas‐mediated cytototxicity

Contact Info

Product

Resources

About