Death-inducing functions of ligands of the tumor necrosis factor family: a Sanhedrin verdict

Wallach, David; Kovalenko, Andrew; Varfolomeev, Eugene; Boldin, Mark

doi:10.1016/s0952-7915(98)80166-0

Cited by 72 publications

(35 citation statements)

References 94 publications

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“…As such, it possesses a structure reminiscent of adapter proteins that bridge domain families, such as Fas-associated death domain protein/mediator of receptor-induced toxicity-1 which is the only protein encoded in the human genome to combine a DD with a DED, and RIP-associated protein with a death domain/CASP2 and RIPK1 domain-containing adaptor with a death domain, the only protein that possesses both a CARD and a DD (reviewed in Ref. 36). ASC is capable of collaborating with certain members of the PAAD family to induce either NF-B activity or procaspase-1 activation (35,37).…”

Section: Discussionmentioning

confidence: 99%

“…For example, ASC and other PAAD family proteins suppressed IL-1␤ secretion induced by LPS (which binds Toll-like receptor (TLR) 2 and TLR4) and TNF, suggesting the existence of cross-talk between these caspase-1 activation pathways. In this regard, both TLRs and TNFRs use TNFR-associated factor (TRAF) family proteins for signal transduction (36). TRAFs bind Cardiak, linking these pathways to caspase-1 activation (11,42).…”

Section: Discussionmentioning

confidence: 99%

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Apoptosis-Associated Speck-Like Protein Containing a Caspase Recruitment Domain Is a Regulator of Procaspase-1 Activation

Stehlik

Lee

Dorfleutner

et al. 2003

The Journal of Immunology

214

178

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Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/target of methylation-induced silencing/PYCARD represents one of only two proteins encoded in the human genome that contains a caspase recruitment domain (CARD) together with a pyrin, AIM, ASC, and death domain-like (PAAD)/PYRIN/DAPIN domain. CARDs regulate caspase family proteases. We show here that ASC binds by its CARD to procaspase-1 and to adapter proteins involved in caspase-1 activation, thereby regulating cytokine pro-IL-1β activation by this protease in THP-1 monocytes. ASC enhances IL-1β secretion into the cell culture supernatants, at low concentrations, while suppressing at high concentrations. When expressed in HEK293 cells, ASC interferes with Cardiak/Rip2/Rick-mediated oligomerization of procaspase-1 and suppresses activation this protease, as measured by protease activity assays. Moreover, ASC also recruits procaspase-1 into ASC-formed cytosolic specks, separating it from Cardiak. We also show that expression of the PAAD/PYRIN family proteins pyrin or cryopyrin/PYPAF1/NALP3 individually inhibits IL-1β secretion but that coexpression of ASC with these proteins results in enhanced IL-1β secretion. However, expression of ASC uniformly interferes with caspase-1 activation and IL-1β secretion induced by proinflammatory stimuli such as LPS and TNF, suggesting pathway competition. Moreover, LPS and TNF induce increases in ASC mRNA and protein expression in cells of myeloid/monocytic origin, revealing another level of cross-talk of cytokine-signaling pathways with the ASC-controlled pathway. Thus, our results suggest a complex interplay of the bipartite adapter protein ASC with PAAD/PYRIN family proteins, LPS (Toll family receptors), and TNF in the regulation of procaspase-1 activation, cytokine production, and control of inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Apoptosis-Associated Speck-Like Protein Containing a Caspase Recruitment Domain Is a Regulator of Procaspase-1 Activation

Stehlik

Lee

Dorfleutner

et al. 2003

The Journal of Immunology

214

178

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“…4 We examined the status of the two active isoforms a and b of caspase -8, 35 before and after TNF treatment of MCF7 cells and cl.1001. Data depicted in Figure 1B indicate that although the two isoforms (corresponding to the bands of 53 and 55 kDa ) were equally expressed, TNF treatment (100 ng/ mL ) resulted in the generation of cleaved intermediate products of 43 and 41 kDa, ( corresponding to caspases -8 a and b isoforms, respectively ), only in TNF -sensitive MCF7 cells.…”

Section: Failure Of Tnf To Induce Pro -Caspase -8 Cleavage In Tnf -Rementioning

confidence: 99%

“…4 Among these molecules, TRADD (TNFR1-associated death domain) specifically interacts with TNFR1 via its death domain motif. 5 TRADD is also able to directly interact with FADD ( Fas -associated death domain ) to induce apoptosis and with TRAF2 ( TNF receptor-associated factor 2 ) and RIP (Receptor Interacting Protein ) to activate NF -B and SAPK / JNK pathways.…”

mentioning

confidence: 99%

Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: Role of caspase-8 and mitochondria

et al. 2002

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In the present study, we have investigated the mechanisms by which the restoration of wild -type ( wt ) p53 functions in p53 mutant cells increases their susceptibility to the cytotoxic action of tumor necrosis factor ( TNF ). Our data indicate that the resistance of p53 -mutated cl.1001 cells to TNF -induced cell death was not due to a defect in the expression of TRADD and FADD, yet correlated with a reduced caspase -8 activation as well as a deficient mitochondrial membrane permeabilization. Moreover, cl.1001 cells failed to translocate the mitochondrial AIF and cytochrome c to the nucleus and to the cytosol, respectively, in response to TNF. Sensitization of these cells, following infection with a recombinant adenovirus encoding wtp53, to TNF -induced cytotoxicity resulted in the restoration of caspase -8 cleavage and the reestablishment of mitochondrial signs of apoptosis. These findings suggest that the crosstalk between p53 and TNF -induced cell death depends on mitochondria and that the combination of TNF and Adwtp53 may be a potential strategy to sensitize mutant p53 TNF -resistant tumors to the cytotoxic action of this cytokine.

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“…14 The cell death pathway activated by TNF-family death receptors is sometimes referred to as the 'extrinsic' pathway for apoptosis, 7 and it involves caspase-8 as the apical protease. 15,16 In contrast, the apical protease in the mitochondrial pathway is caspase-9.…”

Section: Introductionmentioning

confidence: 99%

Synthetic triterpenoids activate a pathway for apoptosis in AML cells involving downregulation of FLIP and sensitization to TRAIL

et al. 2003

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Acute myelogenous leukemia (AML) remains a deadly disease for most adult patients, due primarily to the emergence of chemoresistant cells. Defects in apoptosis pathways make important contributions to chemoresistance, suggesting a need to restore apoptosis sensitivity or to identify alternative pathways for apoptosis induction. Triterpenoids represent a class of naturally occurring and synthetic compounds with demonstrated antitumor activity, including 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and its methyl ester (CDDO-m). We explored the effects of CDDO and CDDO-m in vitro on established AML cell lines (HL-60, U937, AML-2) and on freshly isolated AML blasts. CDDO and CDDO-m reduced the viability of all AML cell lines tested in a dose-dependent manner, with effective doses for killing 50% of cells (ED 50 ) within 48 h of B1 and 0.5 lM, respectively. CDDO or CDDO-m also induced substantial increases in cell death in five out of 10 samples of primary AML blasts. Cell death induced by CDDO and CDDO-m was attributed to apoptosis, based on characteristic cell morphology and evidence of caspase activation. Immunoblot analysis demonstrated proteolytic processing of caspase-3, -7, and -8, but not caspase-9, suggesting the involvement of the 'extrinsic' pathway, linked to apoptosis induction by TNF-family death receptors. Accordingly, CDDO and CDDO-m induced concentration-dependent reductions in the levels of FLIP protein, an endogenous antagonist of caspase-8, without altering the levels of several other apoptosis-relevant proteins. Reductions in FLIP were rapid, detectable within 3 h after exposure of AML cell lines to CDDO or CDDO-m. CDDO and CDDO-m also sensitized two of four leukemia lines to TRAIL, a TNF-family death ligand. The findings suggest that synthetic triterpenoids warrant further investigation in the treatment of AML, alone or in combination with TRAIL or other immunebased therapies.

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Death-inducing functions of ligands of the tumor necrosis factor family: a Sanhedrin verdict

Cited by 72 publications

References 94 publications

Apoptosis-Associated Speck-Like Protein Containing a Caspase Recruitment Domain Is a Regulator of Procaspase-1 Activation

Apoptosis-Associated Speck-Like Protein Containing a Caspase Recruitment Domain Is a Regulator of Procaspase-1 Activation

Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: Role of caspase-8 and mitochondria

Synthetic triterpenoids activate a pathway for apoptosis in AML cells involving downregulation of FLIP and sensitization to TRAIL

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