Abstract
Autophagic or necrotic cell death (ACD and NCD, respectively), studied in the model organism Dictyostelium which offers unique advantages, require triggering by the same differentiation-inducing factor DIF-1. To initiate these two types of cell death, does DIF-1 act through only one or through two distinct recognition structures? Such distinct structures may recognize distinct motifs of DIF-1. To test this albeit indirectly, DIF-1 was modified at one or two of several positions, and the corresponding derivatives were tested for their abilities to induce ACD or NCD. The results strongly indicated that distinct biochemical motifs of DIF-1 were required to trigger ACD or NCD, and that these motifs were separately recognized at the onset of ACD or NCD. In addition, both ACD and NCD were induced more efficiently by DIF-1 than by either its precursors or its immediate catabolite. These results showed an unexpected relation between a differentiation factor, the cellular structures that recognize it, the cell death types it can trigger and the metabolic state of the cell. The latter seems to guide the choice of the signaling pathway to cell death, which in turn imposes the cell death type and the recognition pattern of the differentiation factor.
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Abbreviations
- ACD:
-
autophagic cell death
- DIF-1:
-
differentiation-inducing factor-1
- NCD:
-
necrotic cell death
- ROS:
-
reactive oxygen species
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Acknowledgements
We thank Professor Robert R Kay (MRC Laboratory of Molecular Biology, Cambridge, UK) for an essential suggestion leading to this work, and E Tresse, C Giusti and L Leserman for advice. This work was supported through institutional grants by INSERM and CNRS, and through specific grants by Agence Nationale pour la Recherche (DictyDeath ANR-05-BLAN-0333-01), the European Community (FP6 STREP TransDeath LSHG-CT-2004-511983), the Ministère pour la Recherche (ACI BCMS174), Cancéropôle PACA and Association pour la Recherche sur le Cancer.
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Luciani, M., Kubohara, Y., Kikuchi, H. et al. Autophagic or necrotic cell death triggered by distinct motifs of the differentiation factor DIF-1. Cell Death Differ 16, 564–570 (2009). https://doi.org/10.1038/cdd.2008.177
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DOI: https://doi.org/10.1038/cdd.2008.177
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