Bin1 Interacts with and Restrains the DNA End-Binding Protein Complex Ku
Open accessAbstract
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.
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The BAR domain is known as a binding platform for several protein-protein interactions.
“However, the BAR domain is also known as a binding platform for several protein-protein interactions (37,38), suggesting that BACE1 is a novel cargo protein of BIN1 that is sorted from early endosomes to late endosomes/lysosomes.”
From BIN1 regulates BACE1 intracellular trafficking and amyloid-β production (2016) · cites this paper as [38]
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- Authors
- Ramalingam, A., Farmer, G. E., Stamato, T., & Prendergast, G. C.
- Affiliations
- Lankenau Institute for Medical Research (US)
- DuPont (United States) (US)
- Thomas Jefferson University (US)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2007-08
- Volume
- 6
- Issue
- 15
- Pages
- 1914-1918
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2051388309
- Cited by
- 18
- References
- 36
- Citations by year
- 2025: 3 · 2023: 1 · 2021: 1 · 2019: 2 · 2016: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA082222, R01CA100123, R01CA109542, CA 82222)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- BIN1, Ku70, Ku80, BAR domain, protein-protein interaction, telomere maintenance, DNA end binding, DNA repair, apoptosis, Schizosaccharomyces pombe, telomere length
- MeSH terms
- Ku Autoantigen, Animals, Carrier Proteins, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Nuclear Proteins, Protein Binding, Schizosaccharomyces, Signal Transduction, Tumor Suppressor Proteins, Schizosaccharomyces pombe Proteins, Antigens, Nuclear, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice
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