title: Scythe cleavage during Fas (APO-1)-and staurosporine-mediated apoptosis.
abstract: Scythe is a nuclear protein that has been implicated in the apoptotic process in Drosophila melanogaster; however, its role in apoptosis of mammalian cells is not fully elucidated. Here we show that cleavage of Scythe by caspase-3 occurs after activation of both the extrinsic (i.e. Fas/APO-1-mediated) and the intrinsic (i.e. staurosporine-induced) apoptosis pathway. Moreover, this caspase-dependent cleavage correlates with Scythe translocation from the nucleus to the cytosol. We also show that cytosolic re-localization of Scythe is required for Fas/APO-1-triggered phosphatidylserine (PS) exposure, a signal for macrophage clearance of apoptotic cells. Our data suggest that Scythe cleavage may represent a marker for caspase-3 activation and implicate cytosolic re-localization of Scythe in the pathway of PS exposure.
authors.affiliation: Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Giulio
authors.initials: G
authors.lastname: Preta
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C092009:BAG6 protein, human; D004791:Enzyme Inhibitors; D018832:Molecular Chaperones; D010718:Phosphatidylserines; D019014:fas Receptor; D053148:Caspase 3; D019311:Staurosporine