Sepantronium bromide (YM155) induces disruption of the ILF3/p54(nrb) complex, which is required for survivin expression

YM155, a small-molecule survivin suppressant, specifically binds to the transcription factor ILF3, which regulates the expression of survivin[1]. In this experiment we have demonstrated that p54(nrb) binds to the survivin promoter and regulates survivin expression. p54(nrb) forms a complex with ILF3...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2012-09, Vol.425 (4), p.711-716
Main Authors: Yamauchi, Tomohiro, Nakamura, Naoto, Hiramoto, Masashi, Yuri, Masatoshi, Yokota, Hiroyuki, Naitou, Masanori, Takeuchi, Masahiro, Yamanaka, Kentaro, Kita, Aya, Nakahara, Takahito, Kinoyama, Isao, Matsuhisa, Akira, Kaneko, Naoki, Koutoku, Hiroshi, Sasamata, Masao, Kobori, Masato, Katou, Masao, Tawara, Shuichi, Kawabata, Shigeki, Furuichi, Kiyoshi
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - drug effects
Cell Line, Tumor
Cell Nucleolus - metabolism
E2F1 Transcription Factor - metabolism
E2F2 Transcription Factor - metabolism
HEK293 Cells
Humans
Imidazoles - pharmacology
Inhibitor of Apoptosis Proteins - biosynthesis
Inhibitor of Apoptosis Proteins - genetics
Naphthoquinones - pharmacology
Nuclear Factor 90 Proteins - antagonists & inhibitors
Nuclear Factor 90 Proteins - metabolism
Nuclear Matrix-Associated Proteins - antagonists & inhibitors
Nuclear Matrix-Associated Proteins - metabolism
Octamer Transcription Factors - antagonists & inhibitors
Octamer Transcription Factors - metabolism
Promoter Regions, Genetic
Protein Binding
RNA-Binding Proteins - antagonists & inhibitors
RNA-Binding Proteins - metabolism
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Summary:YM155, a small-molecule survivin suppressant, specifically binds to the transcription factor ILF3, which regulates the expression of survivin[1]. In this experiment we have demonstrated that p54(nrb) binds to the survivin promoter and regulates survivin expression. p54(nrb) forms a complex with ILF3, which directly binds to YM155. YM155 induces disruption of the ILF3/p54(nrb) complex, which results in a different subcellular localization between ILF3 and p54(nrb). Thus, identification of molecular targets of YM155 in suppression of the survivin pathway, might lead to development of its use as a novel potential target in cancers.
ISSN:1090-2104
DOI:10.1016/j.bbrc.2012.07.103