title: The antitumor agent doxorubicin binds to Fanconi anemia group F protein.
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.
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kusayanagi
authors.forename: Senko
authors.initials: S
authors.lastname: Tsukuda
authors.forename: Satomi
authors.initials: S
authors.lastname: Shimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Manita
authors.forename: Kanako
authors.initials: K
authors.lastname: Iwakiri
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamisuki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takakusagi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kouji
authors.initials: K
authors.lastname: Kuramochi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakazaki
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D052219:Fanconi Anemia Complementation Group F Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D019151:Peptide Library; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D000970:Antineoplastic Agents; D052236:Fanconi Anemia Complementation Group D2 Protein; D052219:Fanconi Anemia Complementation Group F Protein; D019151:Peptide Library; D011994:Recombinant Proteins; D004317:Doxorubicin