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Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression
| Title: | Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression |
| Authors: | Mafy, Noushaba Nusrat Browse this author | | Matsuo, Kazuya Browse this author | | Hiruma, Shota Browse this author | | Uehara, Ryota Browse this author | | Tamaoki, Nobuyuki Browse this author →KAKEN DB |
| Issue Date: | 29-Jan-2020 |
| Publisher: | American Chemical Society |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 142 |
| Issue: | 4A |
| Start Page: | 1763 |
| End Page: | 1767 |
| Publisher DOI: | 10.1021/jacs.9b12782 |
| Abstract: | Interfering with mitosis is a potential cancer therapy strategy. However, the lack of controllability of antimitotic drugs in cell growth suppression causes severe side effects and limits their clinical utility. Herein, we developed an azobenzene-based photoswitchable inhibitor of CENP-E, a mitotic kinesin required for chromosome transportation. The new inhibitor enabled reversible photoswitching of CENP-E activity with similar to 10-fold change in IC50 between cis and trans photoisomerization states both in vitro and in living cells. It also enabled repeatable photoswitching of CENP-E-dependent chromosome congression and hence mitotic progression with UV/vis light illumination cycles. Using this technique, we could specify the exact process of mitotic progression in which CENP-E plays an indispensable role. Our data demonstrate the power of a photochemical approach for highly controllable mitotic interference as well as for discovery of precise molecular functions in dynamic cellular processes. |
| Rights: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/jacs.9b12782 . |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/80343 |
| Appears in Collections: | 電子科学研究所 (Research Institute for Electronic Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 玉置 信之
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