Bin1 interacts with and restrains the DNA end-binding protein complex Ku.
The Bin1 gene encodes a BAR adapter protein that suppresses cancer by poorly defined mechanisms. In an effort to gain insights, we identified cellular proteins that form biochemical complexes with Bin1 protein. Here we report that Bin1 physically binds to Ku, a DNA end-binding protein that functions in telomere maintenance, apoptosis, and DNA repair. Both Ku70 and Ku80 were purified from human and murine cell extracts using the Bin1 BAR domain as an affinity matrix. A BAR domain mutation that destroys antioncogenic activity completely abolished Ku binding, supporting functional relevance. To further evaluate meaning, we investigated interactions between the Bin1 homolog hob1+ and the Ku homologs pku70+ and pku80+ in fission yeast. Notably, deleting pku70+ or pku80+ relieved the survival defect displayed by hob1delta cells after treatment with the DNA damaging agent phleomycin, suggesting that hob1+ may restrain Ku. Consistent with this notion, telomere length was altered in hob1delta cells. The potential relevance of Bin1-Ku interaction to cancer are discussed in light of these findings.
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
Arivudainambi
A
Ramalingam
George E
GE
Farmer
Thomas D
TD
Stamato
George C
GC
Prendergast
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; C101410:BIN1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D025521:Tumor Suppressor Proteins; C491080:hob1 protein, S pombe; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen