2024-03-28T10:06:32Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/803432022-11-17T02:08:08Zhdl_2115_20057hdl_2115_148Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic ProgressionMafy, Noushaba NusratMatsuo, KazuyaHiruma, ShotaUehara, Ryota1000000344218Tamaoki, Nobuyukiopen accessThis 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 .425Interfering 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.American Chemical Society2020-01-29engjournal articleAMhttp://hdl.handle.net/2115/80343https://doi.org/10.1021/jacs.9b127820002-7863Journal of the American Chemical Society142417631767https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/80343/1/revised%2bMS-final.pdfapplication/pdf769.1 KB2020-01-29