Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 pull-downs, 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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PMID:Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants. 2835 47

The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved, multifunctional group of cytoprotective co-chaperones. Using structural bioinformatic approaches we identified 7 homologs of the Arabidopsis BAG family. Evaluating knockouts in Arabidopsis of individual BAG family members, we noted that Arabidopsis BAG6 (AtBAG6) knockout lines exhibited a pronounced enhancement of susceptibility to the necrotrophic fungal pathogen Botrytis cinerea. Moreover, we identified a single predicted caspase-1 site that was cleaved by an aspartyl protease (AtAPCB1). Finally, we showed AtBAG6 forms a complex with AtAPCB1 via coupling to a C2 GRAM domain protein (AtBAGP1). This complex and its activation is necessary for triggering pathogen mediated autophagic cell death and host resistance.
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PMID:Processing of AtBAG6 triggers autophagy and fungal resistance. 2712 31