FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade

Wang, S; Xia, Pengyan; Shi, Linqi; Fan, Z

doi:10.1038/cdd.2011.130

Cited by 31 publications

(38 citation statements)

References 36 publications

(46 reference statements)

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“…31 This further underlines the importance of the prime residues for GrM-mediated substrate recognition. For hGrM substrate Fas-associated protein with death domain (FADD), 34 a similar species-specific difference in the cleavage site has been reported. 35 Replacement of the putative P1 and P1' residues in mouse FADD with the corresponding amino acids of human FADD restores cleavage of mouse FADD by both human and mGrM.…”

Section: Substrate Specificitymentioning

confidence: 87%

“…33 In contrast, several other studies have shown that hGrM treatment can lead to phosphatidylserine exposure, DNA fragmentation, targeting of the mitochondria, and caspase activation. 32,34,[44][45][46] Some classical hallmarks of apoptosis (such as phosphatidylserine exposure, DNA fragmentation, and mitochondrial damage) can be the result of caspase activation, so whether or not caspases are activated in response to hGrM may determine whether or not these apoptotic hallmarks are observed. Differences between studies may be due to the method used to produce recombinant hGrM (in Escherichia coli or Pichia pastoris), the applied hGrM concentrations, or the means used for intracellular delivery of hGrM (purified perforin, Pro-Ject protein transfection reagent, adenovirus, or the pore-forming protein streptolysin O (SLO)).…”

Section: Functionsmentioning

confidence: 99%

“…FADDdeficient Jurkat cells are significantly less sensitive to hGrM, and cells expressing an uncleavable FADD-mutant are also more resistant to hGrM-induced apoptosis. 34 hGrM-mediated cleavage of FADD leads to increased self-association of the protein, resulting in the recruitment and activation of procaspase-8 and subsequent activation of the other members of the caspase cascade. 34 Although FADD-deficient cells are less sensitive to hGrM, cell death is not completely impaired, suggesting that other mechanisms are still at play in these cells.…”

Section: Functionsmentioning

confidence: 99%

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Granzyme M: behind enemy lines

Poot

Bovenschen

2014

Cell Death Differ

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The granule-exocytosis pathway is the major mechanism via which cytotoxic lymphocytes eliminate virus-infected and tumor cells. In this pathway, cytotoxic lymphocytes release granules containing the pore-forming protein perforin and a family of serine proteases known as granzymes into the immunological synapse. Pore-formation by perforin facilitates entry of granzymes into the target cell, where they can activate various (death) pathways. Humans express five different granzymes, of which granzymes A and B have been most extensively characterized. However, much less is known about granzyme M (GrM). Recently, structural analysis and advanced proteomics approaches have determined the primary and extended specificity of GrM. GrM functions have expanded over the past few years: not only can GrM efficiently induce cell death in tumor cells, it can also inhibit cytomegalovirus replication in a noncytotoxic manner. Finally, a role for GrM in lipopolysaccharide-induced inflammatory responses has been proposed. In this review, we recapitulate the current status of GrM expression, substrate specificity, functions, and inhibitors.

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Section: Substrate Specificitymentioning

confidence: 87%

Section: Functionsmentioning

confidence: 99%

Section: Functionsmentioning

confidence: 99%

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Granzyme M: behind enemy lines

Poot

Bovenschen

2014

Cell Death Differ

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“…GrM has been shown to cleave Fas-associated protein with death domain (FADD), leading to pro-caspase-8 activation and subsequent mitochondrial damage and apoptosome formation (22,23).…”

mentioning

confidence: 99%

All Human Granzymes Target hnRNP K That Is Essential for Tumor Cell Viability

Domselaar

Quadir²,

Made³

et al. 2012

Journal of Biological Chemistry

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Background: Granzymes have distinct substrate specificities and trigger diverse cell death pathways. Results: All human granzymes can target hnRNP K, which is essential for tumor cell viability. Conclusion: Granzyme-mediated cleavage of hnRNP K contributes to the elimination of tumor cells by cytotoxic lymphocytes. Significance: Elucidating granzyme function provides insights into the role of cytotoxic lymphocytes in tumor immunology.

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“…Fas and FasL belong to the tumour necrosis factor family; their combination enables the Fas-FasL apoptotic pathway. Fas death receptor initiates apoptosis through the assemblages of Fas-associated death domain (FADD) and procaspase-8, subsequent proteolytic cleavage of vital structural substrates, and initiation of the caspase cascade (8). Caspase cascades, which lead to the activation of caspase-3, are essential in the process of apoptosis in the injured spinal cord (9).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

Chen

Lin

Zheng

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. In the present study, we demonstrate that the degeneration of intervertebral discs is caused by ageing and apoptosis of matrix cells. Apoptosis is as essential as the function of proteoglycan synthesis in assessing the possible degeneration of intervertebral discs; paeoniflorin (PF) induces cytoprotective effects on various types of cells. In this study, the function of PF in inhibiting Fas ligand (FasL)-induced apoptosis in annulus fibrosus cells was assessed, and the correlation between apoptosis and the Fas-FasL pathway was determined. Annulus fibrosus cells were derived from the intervertebral discs of 1-month-old Sprague Dawley rats; the cells were characterised by toluidine blue staining and subjected to apoptosis with FasL. PF was diluted to various concentrations and added to annulus fibrosus cells at various times. The impact of PF and FasL on cell apoptosis of annulus fibrosus cells was determined by flow cytometry. Western blot analysis was performed to determine the protein expression levels of Fas and caspase-3. The percentages of apoptotic annulus fibrosus cells as well as the expression levels of caspase-3 and Fas were significantly reduced following treatment with 208, 20.8 or 2.08 µM PF. PF inhibits the activation of the Fas-FasL signal pathway and decreases FasL-induced apoptosis of annulus fibrosus cells.

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FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade

Cited by 31 publications

References 36 publications

Granzyme M: behind enemy lines

Granzyme M: behind enemy lines

All Human Granzymes Target hnRNP K That Is Essential for Tumor Cell Viability

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

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