Small Molecule Inhibition of UBE2T/FANCL-mediated Ubiquitylation in the Fanconi Anemia Pathway
| Autor: | Cornwell, Matthew J, Thomson, Graeme J, Coates, Julia, Belotserkovskaya, Rimma, Waddell, Ian D, Jackson, Stephen P, Galanty, Yaron |
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| Přispěvatelé: | Jackson, Stephen [0000-0001-9317-7937], Galanty, Yaron [0000-0001-7167-9004], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
Small Molecule Libraries
congenital hereditary and neonatal diseases and abnormalities Fanconi Anemia hemic and lymphatic diseases Cell Line Tumor Ubiquitin-Conjugating Enzymes Fanconi Anemia Complementation Group L Protein Ubiquitination nutritional and metabolic diseases Humans health care economics and organizations High-Throughput Screening Assays |
| Popis: | The Fanconi anemia pathway orchestrates the repair of DNA inter-strand crosslinks and stalled replication forks. A key step in this pathway is UBE2T and FANCL dependent monoubiquitylation of the FANCD2-FANCI complex. The Fanconi anemia pathway represents an attractive therapeutic target because activation of this pathway has been linked to chemotherapy resistance in several cancers. However, very few selective inhibitors of ubiquitin conjugation pathways are known to date. By using a high-throughput screen compatible assay, we have identified a small molecule inhibitor of UBE2T/FANCL-mediated FANCD2 monoubiquitylation that sensitizes cells to the DNA cross-linking agent, carboplatin. |
| Databáze: | OpenAIRE |
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