XIAP discriminates between type I and type II FAS-induced apoptosis

Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel H.D.; McKenzie, Mark; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Kaufmann, Thomas

doi:10.1038/nature08229

Cited by 424 publications

(365 citation statements)

References 35 publications

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“…Another potential determinant is XIAP. Ablation of the XIAP gene in mice or treatment with a Smac mimetic drug enabled Fas-mediated apoptosis to occur independently of Bid in hepatocytes and B cells (Jost et al, 2009). Moreover, downregulation of XIAP bypassed the requirement for mitochondrial amplification and sensitized type II cells to apoptosis stimulation by FasL, Apo2L/TRAIL or anti-DR5 agonist antibody (Vogler et al, 2008;Varfolomeev et al, 2009).…”

Section: Apoptosis Signaling By Apo2l/trailmentioning

confidence: 99%

New insights into apoptosis signaling by Apo2L/TRAIL

2010

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Section: Apoptosis Signaling By Apo2l/trailmentioning

confidence: 99%

New insights into apoptosis signaling by Apo2L/TRAIL

2010

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“…lymphocytes) and II (e.g. granulocytes) apoptosis [9]. It has also been implicated in neutrophil survival mediated by G-CSF [10] and is degraded in oxidant-induced neutrophil apoptosis [11].…”

Section: Introductionmentioning

confidence: 99%

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

et al. 2010

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Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g. R-roscovitine) have been shown to induce neutrophil apoptosis and enhance the resolution of inflammation. Interestingly, NF-jB and MAPK pathways and key endogenous survival proteins (typified by Mcl-1) are involved in the regulation of neutrophil apoptosis and, in cancer-cell lines, have been implicated as possible targets of CDK inhibitors. Here, we demonstrate that R-roscovitine over-rides TNF-a and LPS-induced survival (determined by morphological examination and binding of fluorescently labelled annexin-V) of isolated peripheral blood neutrophils. This effect did not appear to be mediated via effects on early markers of neutrophil activation (e.g. surface marker expression, shape change, aggregation and superoxide anion generation), by direct inhibition of NF-jB activation (assessed by cytoplasmic IjBa proteolysis and NF-jB p65 subunit translocation) and ERK activation (determined by specific ERK phosphorylation) but due to down-regulation (at protein and mRNA level) of the survival protein Mcl-1 but not the pro-apoptotic bcl-2 homologue Bim. These findings suggest that key endogenous survival proteins may be the targets of CDK inhibitors and consequently may be of critical importance in the resolution of inflammation.

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“…6 In type II apoptotic cells, caspase-8 activation at the DISC is inhibited by the caspase-3 inhibitor x-linked inhibitor of apoptosis (XIAP) and cellular FLICE inhibitory protein (cFLIP). [6][7][8] Type II cells require the mitochondrial pathway to fully initiate the cell death program via caspase-8 activation at the outer mitochondrial membrane that cleaves Bid to tBid. 9 tBid triggers the oligomerization of Bax/Bak, which initiates mitochondrial outer membrane permeabilization, cytochrome c release and activation of caspase-9.…”

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confidence: 99%

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

et al. 2016

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Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in Nlrp3 − / − cells. The activation of caspase-8 during extrinsic apoptosis induced by TNFα/cycloheximide (TNFα/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1β secretion in response to TNFα/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNFα/ CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not Nlrp3 − / − or ASC − / − mice following ureteric unilateral obstruction in vivo. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells.

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XIAP discriminates between type I and type II FAS-induced apoptosis

Cited by 424 publications

References 35 publications

New insights into apoptosis signaling by Apo2L/TRAIL

New insights into apoptosis signaling by Apo2L/TRAIL

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

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