The antitumor agent doxorubicin binds to Fanconi anemia group F protein
The antitumor agent doxorubicin binds to Fanconi anemia group F protein
复制标题
抗肿瘤剂阿霉素与范可尼贫血 F 组蛋白结合
DOI：
10.1016/j.bmc.2012.09.015
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Sugawara F
中科院分区：
文献类型：
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作者：
Kusavanagi T;Tsukuda S;Shimura S;Manita D;Iwakiri K;Kamisuki S;Takakusagi Y;Takeuchi T;Kuramochi K;Nakazaki A;Sakaguchi K;Kobayashi S;Sugawara F
多柔比星是一种常用的肿瘤化疗药物，与顺铂联用具有协同抗肿瘤作用。然而，这种协同作用的机制仍然不清楚。在这里，我们采用了一种改进的T7噬菌体展示筛选方法，以确定范可尼贫血F组蛋白（FANCF）作为阿霉素结合蛋白。FANCF与阿霉素的相互作用通过pull-down分析和SPR分析证实。FANCF是Fanconi贫血复合物的一种组分，其使Fanconi贫血组的D2蛋白单泛素化，作为对DNA交联剂如顺铂的细胞应答。我们观察到，单泛素化被多柔比星处理抑制。
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.