Ku70 suppresses the apoptotic translocation of Bax to mitochondria.
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.
Sawada
Motoshi
M
Blood Research Institute, The Blood Center of South Eastern Wisconsin, 8727 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Sun
Weiyong
W
Hayes
Paulette
P
Leskov
Konstantin
K
Boothman
David A
DA
Matsuyama
Shigemi
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000235:genetics; D051028:bcl-2-Associated X Protein
D029681:Arabidopsis Proteins; C494826:BAX protein, human; C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; C463462:KU70 protein, Arabidopsis; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein