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

Tomohiro Yamauchi; Naoto Nakamura; Masashi Hiramoto; Masatoshi Yuri; Hiroyuki Yokota; Masanori Naitou; Masahiro Takeuchi; Kentaro Yamanaka; Aya Kita; Takahito Nakahara; Isao Kinoyama; Akira Matsuhisa; Naoki Kaneko; Hiroshi Koutoku; Masao Sasamata; Masato Kobori; Masao Katou; Shuichi Tawara; Shigeki Kawabata; Kiyoshi Furuichi

doi:10.1016/j.bbrc.2012.07.103

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

Biochem Biophys Res Commun. 2012 Sep 7;425(4):711-6. doi: 10.1016/j.bbrc.2012.07.103. Epub 2012 Jul 27.

Affiliation

¹ Drug Discovery Research, Astellas Pharma, Inc., Tsukuba-shi, Ibaraki, Japan. tomohiro.yamauchi@astellas.com

PMID: 22842455
DOI: 10.1016/j.bbrc.2012.07.103

Abstract

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.

MeSH terms

Active Transport, Cell Nucleus / drug effects
Cell Line, Tumor
Cell Nucleolus / metabolism
DNA-Binding Proteins
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
Survivin

Substances

BIRC5 protein, human
DNA-Binding Proteins
E2F1 Transcription Factor
E2F1 protein, human
E2F2 Transcription Factor
E2F2 protein, human
ILF3 protein, human
Imidazoles
Inhibitor of Apoptosis Proteins
NONO protein, human
Naphthoquinones
Nuclear Factor 90 Proteins
Nuclear Matrix-Associated Proteins
Octamer Transcription Factors
RNA-Binding Proteins
Survivin
sepantronium