The identification of functional regions of MEK1 using CRISPR tiling screens
Abstract CRISPR tiling screen is a powerful tool to identify protein regions relevant to its biological function. Understanding the functional relevance of the regions of target protein is of great help for structure-based drug discovery. Studying the drug resistance mechanisms of small-molecule inh...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07966-4 |
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| _version_ | 1849311100335554560 |
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| author | Zhiqiang Zhang Barbara Abreu Jessica L. Brothwood John Alexander Martin J. Sims John F. Lyons Joanne M. Munck Christopher J. Hindley |
| author_facet | Zhiqiang Zhang Barbara Abreu Jessica L. Brothwood John Alexander Martin J. Sims John F. Lyons Joanne M. Munck Christopher J. Hindley |
| author_sort | Zhiqiang Zhang |
| collection | DOAJ |
| description | Abstract CRISPR tiling screen is a powerful tool to identify protein regions relevant to its biological function. Understanding the functional relevance of the regions of target protein is of great help for structure-based drug discovery. Studying the drug resistance mechanisms of small-molecule inhibitors is important for the development and clinical application of the compounds. Using MEK1 and MEK inhibitors as example here, we demonstrate the utility of CRISPR tiling to identify regions essential for cancer cell viability and regions where mutations are resistant to MEK inhibitors. We study the drug resistance mechanisms of the regions and discussed the potential, as well as limitations, of applying the technology to drug development. Our findings demonstrate the value and prompt the utilization of CRISPR tiling technology in structure-based drug discovery. |
| format | Article |
| id | doaj-art-65bfa0faa14b4cb1aae762edb315aa92 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-65bfa0faa14b4cb1aae762edb315aa922025-08-20T03:53:32ZengNature PortfolioCommunications Biology2399-36422025-04-018111510.1038/s42003-025-07966-4The identification of functional regions of MEK1 using CRISPR tiling screensZhiqiang Zhang0Barbara Abreu1Jessica L. Brothwood2John Alexander3Martin J. Sims4John F. Lyons5Joanne M. Munck6Christopher J. Hindley7Astex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAstex PharmaceuticalsAbstract CRISPR tiling screen is a powerful tool to identify protein regions relevant to its biological function. Understanding the functional relevance of the regions of target protein is of great help for structure-based drug discovery. Studying the drug resistance mechanisms of small-molecule inhibitors is important for the development and clinical application of the compounds. Using MEK1 and MEK inhibitors as example here, we demonstrate the utility of CRISPR tiling to identify regions essential for cancer cell viability and regions where mutations are resistant to MEK inhibitors. We study the drug resistance mechanisms of the regions and discussed the potential, as well as limitations, of applying the technology to drug development. Our findings demonstrate the value and prompt the utilization of CRISPR tiling technology in structure-based drug discovery.https://doi.org/10.1038/s42003-025-07966-4 |
| spellingShingle | Zhiqiang Zhang Barbara Abreu Jessica L. Brothwood John Alexander Martin J. Sims John F. Lyons Joanne M. Munck Christopher J. Hindley The identification of functional regions of MEK1 using CRISPR tiling screens Communications Biology |
| title | The identification of functional regions of MEK1 using CRISPR tiling screens |
| title_full | The identification of functional regions of MEK1 using CRISPR tiling screens |
| title_fullStr | The identification of functional regions of MEK1 using CRISPR tiling screens |
| title_full_unstemmed | The identification of functional regions of MEK1 using CRISPR tiling screens |
| title_short | The identification of functional regions of MEK1 using CRISPR tiling screens |
| title_sort | identification of functional regions of mek1 using crispr tiling screens |
| url | https://doi.org/10.1038/s42003-025-07966-4 |
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