<i>Arabidopsis</i>
            Type I Metacaspases Control Cell Death

Coll, Núria S.; Vercammen, Dominique; Smidler, Andrea L.; Clover, Charles; Breusegem, Frank Van; Dangl, Jeffery L.; Epple, Petra

doi:10.1126/science.1194980

Cited by 385 publications

(381 citation statements)

References 32 publications

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“…10,31,32 In contrast, the role of trypanosomatid metacaspases seems to be less certain. Overexpression of full-length TcMCA5 in T. cruzi renders epimastigotes more susceptible to FHS-induced cell death, 20 and Gonzá lez et al 30 have shown that L. major metacaspase can replace yeast metacaspase in its pro-cell death action during ageing.…”

Section: Discussionmentioning

confidence: 99%

“…5 Their substrate specificity is for basic residues at P1 position, making them unable to cleave caspase substrates. 6 Evidences suggest that metacaspases modulate cell death, [7][8][9][10][11] cell cycle progression [12][13][14] and protein aggregation, 15 but there is still controversy about their functions and their relation with caspases. [16][17][18] The fact that metacaspases are not present in humans and fulfil important roles in trypanosomatids make them attractive drug targets, and a first series of inhibitors with trypanocidal activity has been developed recently.…”

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confidence: 99%

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Antagonic activities of Trypanosoma cruzi metacaspases affect the balance between cell proliferation, death and differentiation

2012

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Metacaspases are distant relatives of animal caspases present in plants, fungi and protozoa. At variance with caspases, metacaspases exhibit stringent specificity for basic amino-acid residues and are absolutely dependent on millimolar concentrations of calcium. In the protozoan parasite Trypanosoma cruzi, metacaspases have been suggested to be involved in an apoptosis-like phenomenon upon exposure of the parasite to fresh human serum (FHS). Nuclear relocalization of metacaspases was observed after FHS treatment and overexpression of metacaspase-5 led to enhanced sensitivity to this stimulus. Here we report some biochemical properties of T. cruzi metacaspases. Performing fluorescent-activated cell sorting (FACS) analysis of epimastigotes inducibly overexpressing metacaspase-3, we demonstrate a role for this metacaspase in cell cycle progression, protection of epimastigotes from naturally occurring cell death and differentiation to infective metacyclic trypomastigotes. We also show that regulation of metacaspase-3 activity is important for cell cycle completion inside the mammalian host. On the other hand, inducible overexpression of metacaspase-5 lacking its C-terminal domain caused an apoptotic-like response. These results suggest that the two T. cruzi metacaspases could play an important role in the life cycle and bring to light the close relationship between cell division, death and differentiation in this ancient unicellular eukaryote.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Antagonic activities of Trypanosoma cruzi metacaspases affect the balance between cell proliferation, death and differentiation

2012

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“…Thus, the processed BAG6 generated from aspartyl protease cleavage correlates with plant resistance via autophagy. Several genes have been shown to modulate cell death and potentially alter immune responses in Arabidopsis, including LOL1 (Epple et al, 2003), LSD1 (Torres et al, 2005), and metacaspases (Coll et al, 2010). Premature senescence and spreading lesions also occur in autophagydeficient plants as a result of accumulation of ubiquitinated proteins and with ER stress (Coll et al, 2014;Munch et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

et al. 2016

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The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved group of cochaperones that modulate numerous cellular processes. Previously we found that Arabidopsis thaliana BAG6 is required for basal immunity against the fungal phytopathogen Botrytis cinerea. However, the mechanisms by which BAG6 controls immunity are obscure. Here, we address this important question by determining the molecular mechanisms responsible for BAG6-mediated basal resistance. We show that Arabidopsis BAG6 is cleaved in vivo in a caspase-1-like-dependent manner and via a combination of pulldowns, mass spectrometry, yeast two-hybrid assays, and chemical genomics, we demonstrate that BAG6 interacts with a C2 GRAM domain protein (BAGP1) and an aspartyl protease (APCB1), both of which are required for BAG6 processing. Furthermore, fluorescence and transmission electron microscopy established that BAG6 cleavage triggers autophagy in the host that coincides with disease resistance. Targeted inactivation of BAGP1 or APCB1 results in the blocking of BAG6 processing and loss of resistance. Mutation of the cleavage site blocks cleavage and inhibits autophagy in plants; disease resistance is also compromised. Taken together, these results identify a mechanism that couples an aspartyl protease with a molecular cochaperone to trigger autophagy and plant defense, providing a key link between fungal recognition and the induction of cell death and resistance.

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“…The hypersensitive response is often used as a visible measure of an effective defense response and a hallmark of immunity, however, caution must be taken as the hypersensitive response is not essential and immunity can be achieved without an outcome of cell death [14].…”

Section: Host Immunity In Plant-parasite Interactionsmentioning

confidence: 99%

“…The putative defense gene PR-1a is one example where failure to properly account for 14 developmental context could lead to misinterpretation. PR-1a was up-regulated systemically in leaves of tomato plants infested with root-knot nematodes, but there was no differential expression in root tissues [34].…”

Section: Defense Marker Genes: a Question Of Contextmentioning

confidence: 99%