The antitumor agent doxorubicin binds to Fanconi anemia group F protein |
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| Authors: | Tomoe Kusayanagi Senko Tsukuda Satomi Shimura Daisuke Manita Kanako Iwakiri Shinji Kamisuki Yoichi Takakusagi Toshifumi Takeuchi Kouji Kuramochi Atsuo Nakazaki Kengo Sakaguchi Susumu Kobayashi Fumio Sugawara |
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| Affiliation: | 1. Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan;2. Department of Medicinal and Life Science, Faculty of Pharmaceutical, Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan;3. Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan |
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| Abstract: | Doxorubicin, a commonly used cancer chemotherapy agent, elicits several potent biological effects, including synergistic-antitumor activity in combination with cisplatin. However, the mechanism of this synergism remains obscure. Here, we employed an improved T7 phage display screening method to identify Fanconi anemia group F protein (FANCF) as a doxorubicin-binding protein. The FANCF-doxorubicin interaction was confirmed by pull-down assay and SPR analysis. FANCF is a component of the Fanconi anemia complex, which monoubiquitinates D2 protein of Fanconi anemia group as a cellular response against DNA cross-linkers such as cisplatin. We observed that the monoubiquitination was inhibited by doxorubicin treatment. |
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