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M706419200v1
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Papers In Press, published online ahead of print December 3, 2007
J. Biol. Chem, 10.1074/jbc.M706419200
Submitted on August 3, 2007
Accepted on December 3, 2007

Scythe regulates apoptosis inducing factor stability during endoplasmic reticulum stress induced apoptosis

Fabienne Desmots, Helen R. Russell, Denis Michel, and Peter J. McKinnon

Homéostasie Intracellulaire des protéines, UMR 6026-CNRS, Rennes 35042

Corresponding Author: fabienne.desmots{at}univ-rennes1.fr

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.


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J. H. Kwak, S. I. Kim, J. K. Kim, and M. E. Choi
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[Abstract] [Full Text] [PDF]


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