RRC ID 48750
Author Ge Y, Cai YM, Bonneau L, Rotari V, Danon A, McKenzie EA, McLellan H, Mach L, Gallois P.
Title Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis.
Journal Cell Death Differ.
Abstract Programmed cell death (PCD) is used by plants for development and survival to biotic and abiotic stresses. The role of caspases in PCD is well established in animal cells. Over the past 15 years, the importance of caspase-3-like enzymatic activity for plant PCD completion has been widely documented despite the absence of caspase orthologues. In particular, caspase-3 inhibitors blocked nearly all plant PCD tested. Here, we affinity-purified a plant caspase-3-like activity using a biotin-labelled caspase-3 inhibitor and identified Arabidopsis thaliana cathepsin B3 (AtCathB3) by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Consistent with this, recombinant AtCathB3 was found to have caspase-3-like activity and to be inhibited by caspase-3 inhibitors. AtCathepsin B triple-mutant lines showed reduced caspase-3-like enzymatic activity and reduced labelling with activity-based caspase-3 probes. Importantly, AtCathepsin B triple mutants showed a strong reduction in the PCD induced by ultraviolet (UV), oxidative stress (H2O2, methyl viologen) or endoplasmic reticulum stress. Our observations contribute to explain why caspase-3 inhibitors inhibit plant PCD and provide new tools to further plant PCD research. The fact that cathepsin B does regulate PCD in both animal and plant cells suggests that this protease may be part of an ancestral PCD pathway pre-existing the plant/animal divergence that needs further characterisation.
Volume 23(9)
Pages 1493-501
Published 2016-9-1
DOI 10.1038/cdd.2016.34
PII cdd201634
PMID 27058316
PMC PMC5072426
MeSH Amino Acid Sequence Apoptosis / drug effects Apoptosis / radiation effects Arabidopsis / enzymology* Arabidopsis / growth & development Arabidopsis Proteins / antagonists & inhibitors Arabidopsis Proteins / isolation & purification Arabidopsis Proteins / metabolism* Caspase Inhibitors / pharmacology* Cathepsin B / antagonists & inhibitors Cathepsin B / classification Cathepsin B / metabolism* Chromatography, High Pressure Liquid Endoplasmic Reticulum Stress / drug effects Hydrogen Peroxide / toxicity Oxidative Stress / drug effects Paraquat / toxicity Phylogeny Plants, Genetically Modified / enzymology Plants, Genetically Modified / growth & development Recombinant Proteins / biosynthesis Recombinant Proteins / chemistry Recombinant Proteins / isolation & purification Seedlings / drug effects Seedlings / growth & development Seedlings / radiation effects Tandem Mass Spectrometry Ultraviolet Rays
IF 8.0
Times Cited 6
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Arabidopsis / Cultured plant cells, genes pda02452 pda06461