title: Interaction of Leukocyte Elastase Inhibitor/L-DNase II with BCL-2 and BAX.
abstract: Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis.
authors.affiliation: INSERM UMRS 1138, Centre de Recherches des Cordeliers, Université Paris Descartes, Université Pierre et Marie Curie, 15 Rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Imène
authors.initials: I
authors.lastname: Jaadane
authors.affiliation: INSERM UMRS 1138, Centre de Recherches des Cordeliers, Université Paris Descartes, Université Pierre et Marie Curie, 15 Rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Atf
authors.initials: A
authors.lastname: Nagbou
authors.affiliation: INSERM UMRS 1138, Centre de Recherches des Cordeliers, Université Paris Descartes, Université Pierre et Marie Curie, 15 Rue de l'Ecole de Médecine, 75006 Paris, France; Hôpital Ophtalmique Jules-Gonin, Avenue de France 15, Case Postale 133, 1000 Lausanne 7, Switzerland.
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.affiliation: INSERM UMRS 1138, Centre de Recherches des Cordeliers, Université Paris Descartes, Université Pierre et Marie Curie, 15 Rue de l'Ecole de Médecine, 75006 Paris, France. Electronic address: alicia.torriglia@inserm.fr.
authors.forename: Alicia
authors.initials: A
authors.lastname: Torriglia
keywords: BAX; BCL-2; Caspase independent cell death; LEI/L-DNase II; Molecular interaction