title: Interleukin enhancer-binding factor 3/NF110 is a target of YM155, a suppressant of survivin.
abstract: Survivin is responsible for cancer progression and drug resistance in many types of cancer. YM155 selectively suppresses the expression of survivin and induces apoptosis in cancer cells in vitro and in vivo. However, the mechanism underlying these effects of YM155 is unknown. Here, we show that a transcription factor, interleukin enhancer-binding factor 3 (ILF3)/NF110, is a direct binding target of YM155. The enhanced survivin promoter activity by overexpression of ILF3/NF110 was attenuated by YM155 in a concentration-dependent manner, suggesting that ILF3/NF110 is the physiological target through which YM155 mediates survivin suppression. The results also show that the unique C-terminal region of ILF3/NF110 is important for promoting survivin expression and for high affinity binding to YM155.
authors.affiliation: Drug Discovery Research, Astellas Pharma, Inc., Tsukuba, Ibaraki, 305-8585, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Hiramoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yuri
authors.forename: Masanori
authors.initials: M
authors.lastname: Naito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Aya
authors.initials: A
authors.lastname: Kita
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakahara
authors.forename: Isao
authors.initials: I
authors.lastname: Kinoyama
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuhisa
authors.forename: Naoki
authors.initials: N
authors.lastname: Kaneko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koutoku
authors.forename: Masao
authors.initials: M
authors.lastname: Sasamata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokota
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kawabata
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furuichi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D047468:Immunoprecipitation; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000077022:Survivin; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C429643:ILF3 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D050779:Nuclear Factor 90 Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; C523798:sepantronium