Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis

Y. Ge, Y.-M. Cai, L. Bonneau, V. Rotari, A. Danon, E. A. McKenzie, H. McLellan, L. Mach, P. Gallois (Lead / Corresponding author)

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73 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1493-1501
Number of pages9
JournalCell Death & Differentiation
Issue number9
Early online date8 Apr 2016
Publication statusPublished - 1 Sept 2016


  • Amino acid sequence
  • Apoptosis
  • Arabidopsis
  • Arabidopsis proteins
  • Caspase inhibitors
  • Cathepsin B
  • Chromatography, High Pressure Liquid
  • Endoplasmic reticulum stress
  • Hydrogen peroxide
  • Oxidative stress
  • Paraquat
  • Phylogeny
  • Plants, Genetically modified
  • Recombinant proteins
  • Seedlings
  • Tandem mass spectrometry
  • Ultraviolet rays
  • Journal article


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