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

Mafy, Noushaba Nusrat; Matsuo, Kazuya; Hiruma, Shota; Uehara, Ryota; Tamaoki, Nobuyuki

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

Mafy, Noushaba Nusrat; Matsuo, Kazuya; Hiruma, Shota et al.

Journal of the American Chemical Society, 2020, 142(4A), 1763-1767

Permalink : https://hdl.handle.net/2115/80343

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アクセス権	open access
URI	https://hdl.handle.net/2115/80343
タイトル	Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression
著者	Mafy, Noushaba Nusrat ; Matsuo, Kazuya ; Hiruma, Shota ; Uehara, Ryota ; Tamaoki, Nobuyuki
著者名 Mafy, Noushaba Nusrat
著者名 Matsuo, Kazuya
著者名 Hiruma, Shota
著者名 Uehara, Ryota
e-Rad_Researcher 00344218 著者名 Tamaoki, Nobuyuki
言語	英語
発行日	2020-01-29
出版者	American Chemical Society
収録物名	Journal of the American Chemical Society
巻(号)	142(4A)
ページ	1763-1767
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	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 .
PISSN	0002-7863
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1021/jacs.9b12782