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Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression

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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 .
Type: article (author version)
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)

Submitter: 玉置 信之

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