TRAIL receptor-2 signals apoptosis through FADD and caspase-8

Bodmer, Jean-Luc; Holler, Nils; Reynard, Séverine; Vinciguerra, Patrizia; Schneider, Pascal; Juo, Peter; Blenis, Joe; Tschopp, Jürg

doi:10.1038/35008667

Cited by 595 publications

(501 citation statements)

References 17 publications

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“…Finally, sepharose beads were washed four times with RIPA buffer, and the bound proteins were eluted with sodium dodecyl sulfate sample buffer for immunoblot analysis. MCF-7 cells (1 Â 10 7 cells per condition) were treated with TRAIL for 30 min to induce recruitment of FADD and DISC formation as described previously (Bodmer et al, 2000). The cell lysates were immunoprecipitated with anti-FADD antibodies, and the immunoprecipitates were subjected to immunoblot analysis.…”

Section: Immunoprecipitation and Induction Of Discmentioning

confidence: 99%

DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD

Ren

Wang

et al. 2011

Oncogene

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Section: Immunoprecipitation and Induction Of Discmentioning

confidence: 99%

DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD

Ren

Wang

et al. 2011

Oncogene

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“…Upon ligand binding, death receptors dimerize and engage in the formation of the deathinducing signaling complex (DISC), which contains at least the receptor, initiator procaspases 8 or 10, and the protein adaptor Fas-associated death domain or TNFR1-associated death domain. [18][19][20] This provokes the self proteolysis and activation of the initiator caspase, which then directly cleaves and activates effector caspases. [21][22][23] The Bcl-2 family member Bid is cleaved by caspase 8 and targeted to the mitochondria, where it induces cytochrome c release and unleashes the intrinsic apoptotic machinery, providing a direct link between both apoptotic pathways.…”

Section: Introductionmentioning

confidence: 99%

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

López-Hernández¹,

Ortiz²,

Bayón³

et al. 2003

Cell Death Differ

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Certain retinoid-related molecules (RRMs) with agonist or antagonist activities have been described to induce apoptosis in a variety of cancer cell lines and show promise for the treatment of cancer. Similar to other chemotherapeutic drugs, these retinoid analogs have been suggested to induce apoptosis through the intrinsic pathway, which requires the release of cytochrome c from the mitochondria for the effective activation of caspase 9. Expression of a catalytically inactive form of caspase 9, which functions as a dominant negative mutant, inhibits the induction of DEVDase activity and nuclear fragmentation by selective RRMs. Whereas the RRMs could induce the release of cytochrome c in the absence of caspase 9 activity, the later is necessary for the effective release of Smac/Diablo from the mitochondria. Furthermore, overexpression of Bcl-2 or Bcl-X L also inhibits RRM-induced apoptosis. We demonstrate that activation of caspase 2 by the agonist MX2870-1 requires caspase 9 activity and is inhibited by Bcl-2 overexpression. In contrast, the antagonist MX781 induces cleavage of procaspase 2 upstream of mitochondria and independently of caspase 9. Thus, two retinoid analogs with unique characteristics activate two distinct apical caspases (2 or 9) to initiate apoptosis. In addition to caspase-mediated cell death, sustained exposure to the RRMs can also lead to loss of cell viability in cells lacking caspase 9 activity or in cells stimulated in the presence of the caspase inhibitor Z-VADfmk. Moreover, MX2870-1 and MX781 produce cell cycle arrest independently of caspase activity and the retinoid receptors.

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“…31 Apoptosis can also be induced by caspase-8, which signals through membrane-bound death receptors. 32,33 Among the proteins cleaved by caspase-3, PARP is considered relevant for its role in DNA repair and as a marker for caspase activity. 34,35 Grant sponsor: Fondo Europeo de Desarrollo Regional-Comision Interministerial de Ciencia y Técnologia (FEDER-CICYT); Grant number: 1FD97-0934; Grant sponsor: Junta de Extremadura; Grant number: 2PR01A092.…”

mentioning

confidence: 99%

“…31 Apoptosis can also be induced by caspase-8, which signals through membrane-bound death receptors. 32,33 Among the proteins cleaved by caspase-3, PARP is considered relevant for its role in DNA repair and as a marker for caspase activity. 34,35 In previous studies, we suggested that the ERa-dependent PI3K pathway could mediate apoptosis induction by RES in MCF-7 cells.…”

mentioning

confidence: 99%

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

Pozo‐Guisado

Merino

Mulero‐Navarro

et al. 2005

Intl Journal of Cancer

205

143

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Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERa)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kB, were both inhibited by RES. The patterns for NFkB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kB and calpain protease activity. Therefore, Bcl-2 and NF-kB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; caspase; Bcl-2; NF-kB; apoptosis Among natural compounds with beneficial effects on human health, RES (3,4 0 ,5-trihydroxystilbene) has attracted considerable interest. This molecule, present at relevant concentrations in red wine, 1 has been associated with a lower incidence of cardiovascular disease. Different studies have also suggested a beneficial effect of RES in cancer since it inhibits proliferation and promotes death in tumor cell lines of different origins, 2-4 and, in vivo, suppresses the formation of skin 5 and mammary gland 6 tumors in rodent models of carcinogenesis.We, as well as other laboratories, have found that the ability of RES to inhibit cell viability and proliferation in the human breast cancer cell lines MCF-7 and MDA-MB-231 was unrelated to ERa status. 7,8 However, apoptotic cell death was present only in ERapositive MCF-7 and involved cell-specific regulation of the G 1 /S and G 2 /M transitions of the cell cycle. 2,8 RES properties are related to ERa since this compound has estrogenic or antiestrogenic activities depending on its concentration and the phenotype of the target cell. 9,10 ERa, in addition to its nuclear role as a transcription factor, is involved in regulating the PI3K pathway, which controls cell growth, proliferation and apoptosis. [11][12][13] In MCF-7 cells, RES induced a biphasic pattern of PI3K activity that increased at low concentrations and decreased at high concentrations. Activation of downstream PI3K effectors PKB/AKT and GSK-3 closely followed the pattern of PI3K activity. 14 The ...

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TRAIL receptor-2 signals apoptosis through FADD and caspase-8

Cited by 595 publications

References 17 publications

DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD

DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

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