Galig, a novel cell death gene that encodes a mitochondrial protein promoting cytochrome c release.
Fiche publication
Date publication
janvier 2005
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GUITTAUT Michaël
Tous les auteurs :
Duneau M, Boyer-Guittaut M, Gonzalez P, Charpentier S, Normand T, Dubois M, Raimond J, Legrand A
Lien Pubmed
Résumé
Galectin-3 internal gene (Galig) was recently identified as an internal gene transcribed from the second intron of the human galectin-3 gene that is implicated in cell growth, cell differentiation, and cancer development. In this study, we show that galig expression causes morphological alterations in human cells, such as cell shrinkage, cytoplasm vacuolization, nuclei condensation, and ultimately cell death. These alterations were associated with extramitochondrial release of cytochrome c, a known cell death effector. Furthermore, Bcl-xL co-transfection significantly reduced the release of cytochrome c induced by galig expression, suggesting a common pathway between the cytotoxic activity of galig and the anti-apoptotic activity of Bcl-xL. This antagonism was not observed upon co-transfection of Bcl-2 and galig. Galig encodes a mitochondrial-targeted protein named mitogaligin. Structure-activity relationship studies showed that the mitochondrial addressing of mitogaligin relies on an internal sequence that is required and sufficient for the release of cytochrome c and cell death upon cell transfection. Moreover, incubation of isolated mitochondria with peptides derived from mitogaligin induces cytochrome c release. Altogether, these results show that galig is a novel cell death gene encoding mitogaligin, a protein promoting cytochrome c release upon direct interaction with the mitochondria.
Référence
Exp Cell Res. 2005 Jan 15;302(2):194-205.