The conformational modification of serpins transforms Leukocyte Elastase Inhibitor into an endonuclease involved in apoptosis. - Université Pierre et Marie Curie Accéder directement au contenu
Article Dans Une Revue Molecular and Cellular Biology Année : 2007

The conformational modification of serpins transforms Leukocyte Elastase Inhibitor into an endonuclease involved in apoptosis.

Résumé

The best characterized biochemical feature of apoptosis is degradation of genomic DNA into oligonucleosomes. The endonuclease responsible for DNA degradation in caspase-dependent apoptosis is Caspase Activated DNase (CAD). In caspase-independent apoptosis, different endonucleases may be activated according to the cell line and the original insult. Among the known effectors of caspase-independent cell death, L-DNase II (LEI derived DNase II) has been previously characterized by our laboratory. We have thus shown that this endonuclease derives from a serpin super-family member LEI (Leukocyte Elastase Inhibitor) by post-translational modification [Torriglia et al, (1998) Mol. Cell. Biol 18, 3612-3619]. In this work we assessed the molecular mechanism involved in the change of the enzymatic activity of this molecule from an anti-protease to an endonuclease. We report that the cleavage of LEI by elastase at its reactive center loop abolishes its anti-protease activity and leads to a conformational modification that exposes an endonuclease active site and a Nuclear Localization Signal (NLS). This represents a novel molecular mechanism for a complete functional conversion induced by the conformational change of a serpin. We also show that this molecular transformation affects cellular fate and that both endonuclease activity and nuclear translocation of L-DNase II, are needed to induce cell death.
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Dates et versions

inserm-00140748 , version 1 (10-04-2007)

Identifiants

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Laura Padron-Barthe, Chloé Leprêtre, Elisabeth Martin, Marie-France Counis, Alicia Torriglia. The conformational modification of serpins transforms Leukocyte Elastase Inhibitor into an endonuclease involved in apoptosis.. Molecular and Cellular Biology, 2007, pp.10.1128. ⟨10.1128/MCB.01959-06⟩. ⟨inserm-00140748⟩
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