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Originally published In Press as doi:10.1074/jbc.M706419200 on December 3, 2007
J. Biol. Chem., Vol. 283, Issue 6, 3264-3271, February 8, 2008
Scythe Regulates Apoptosis-inducing Factor Stability during Endoplasmic Reticulum Stress-induced Apoptosis*
Fabienne Desmots 1,
Helen R. Russell ,
Denis Michel , and
Peter J. McKinnon
From the
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105 and the UMR 6026, CNRS, Université de Rennes 1, 35042 Rennes Cedex, France
Scythe (BAT3; HLA-B associated transcript 3, Bag 6) is a protein that has been implicated in apoptosis because it can modulate the Drosophila melanogaster apoptotic regulator, Reaper. Mice lacking Scythe show pronounced defects in organogenesis and in the regulation of apoptosis and proliferation during mammalian development. However, the biochemical pathways important for Scythe function are unknown. We report here multiple levels of interaction between Scythe and the apoptogenic mitochondrial intermembrane protein AIF (apoptosis-inducing factor). Scythe physically interacts with AIF and regulates its stability. AIF stability is markedly reduced in Scythe-/- cells, which are more resistant to endoplasmic reticulum stress induced by thapsigargin. Reintroduction of Scythe or overexpression of AIF in Scythe-/- cells restores their sensitivity to apoptosis. Together, these data implicate Scythe as a regulator of AIF.
Received for publication, August 3, 2007
, and in revised form, November 26, 2007.
* This work was supported by the National Institutes of Health and the American Lebanese and Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital and the "Association pour la Recherche sur le Cancer". The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.
1 To whom correspondence should be addressed. Tel.: 33-02-23-23-50-93; Fax: 33-02-23-23-50-52; E-mail: fabienne.desmots{at}univ-rennes1.fr.

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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
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