Article abstract
Nature Cell Biology 5, 320 - 329 (2003)
Published online: 24 March 2003 | doi:10.1038/ncb950
There is a Corrigendum (April 2004) associated with this Article.
There is a Retraction (April 2007) associated with this Article.
Ku70 suppresses the apoptotic translocation of Bax to mitochondria
Motoshi Sawada1,2,4, Weiyong Sun1,2,4, Paulette Hayes1,2, Konstantin Leskov3, David A. Boothman3 & Shigemi Matsuyama1,2
Abstract
Bax induces mitochondrial-dependent cell death signals in mammalian cells. However, the mechanism of how Bax is kept inactive has remained unclear. Yeast-based functional screening of Bax inhibitors from mammalian cDNA libraries identified Ku70 as a new Bax suppressor. Bax-mediated apoptosis was suppressed by overexpression of Ku70 in mammalian cells, but enhanced by downregulation of Ku70. We found that Ku70 interacts with Bax, and that the carboxyl terminus of Ku70 and the amino terminus of Bax are required for this interaction. Bax is known to translocate from the cytosol to mitochondria when cells receive apoptotic stimuli. We found that Ku70 blocks the mitochondrial translocation of Bax. These results suggest that in addition to its previously recognized DNA repair activity in the nucleus, Ku70 has a cytoprotective function in the cytosol that controls the localization of Bax.
- Blood Research Institute, The Blood Center of South Eastern Wisconsin, 8727 Watertown Plank Rd, Milwaukee, WI 53226, USA
- Department of Biochemistry, Medical College of Wisconsin, 8727 Watertown Plank Rd, Milwaukee, WI 53226, USA
- Departments of Radiation Oncology and Pharmacology, Case Western Reserve University and University Hospitals of Cleveland, BRB-326 East, 10900 Euclid Avenue, Cleveland, OH 44106-4942, USA
- These authors contributed equally to this work.
Correspondence to: Shigemi Matsuyama1,2 e-mail: smatsuyama@csew.edu
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