2017 Fiscal Year Final Research Report
Development of therapeutic approaches for cystic fibrosis targeting CFTR ubiquitination
| Project/Area Number |
15H05643
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kwansei Gakuin University |
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Principal Investigator |
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| Research Collaborator |
KAI Hirohumi 熊本大学, 大学院・生命科学研究部, 教授
LUKACS Gergely McGill University, Department of Physiology, Professor
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 嚢胞性線維症 / CFTR / ユビキチン |
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| Outline of Final Research Achievements |
Cystic fibrosis (CF) is a lethal genetic disease caused by mutation of CFTR. CF drug has been developed, but its efficacy remains insufficient because it fails to inhibit the CFTR mutant ubiquitination, which is a degradation signal. Recently, we have identified the novel ubiquitin (Ub) ligases for the CFTR mutant. In this project, we investigated the molecular mechanism of how the Ub ligases stimulate the degradation of CFTR mutant. We discovered that RFFL, a novel Ub ligase for the CFTR, directly and selectively binds to the cytoplasmic region of the CFTR mutant through its disordered regions. Moreover, we developed the assay system that can easily measure the direct interaction between RFFL and the CFTR mutant. This assay system may be useful to discover a novel class of CF drug.
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| Free Research Field |
分子細胞生物学
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