Open AccessInhibition of SNW 1 association with spliceosomal proteins promotes apoptosis in breast cancer cells
Author(s) -
Sato Naoki,
Maeda Masao,
Sugiyama Mai,
Ito Satoko,
Hyodo Toshinori,
Masuda Akio,
Tsunoda Nobuyuki,
Kokuryo Toshio,
Hamaguchi Michinari,
Nagino Masato,
Senga Takeshi
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.366
Subject(s) - spliceosome , rna splicing , gene knockdown , apoptosis , cancer cell , biology , microbiology and biotechnology , cytotoxic t cell , proteomics , rna , cancer , cancer research , chemistry , biochemistry , genetics , gene , in vitro
RNA splicing is a fundamental process for protein synthesis. Recent studies have reported that drugs that inhibit splicing have cytotoxic effects on various tumor cell lines. In this report, we demonstrate that depletion of SNW 1, a component of the spliceosome, induces apoptosis in breast cancer cells. Proteomics and biochemical analyses revealed that SNW 1 directly associates with other spliceosome components, including EFTUD 2 (Snu114) and SNRNP 200 (Brr2). The SKIP region of SNW 1 interacted with the N‐terminus of EFTUD 2 as well as two independent regions in the C‐terminus of SNRNP 200. Similar to SNW 1 depletion, knockdown of EFTUD 2 increased the numbers of apoptotic cells. Furthermore, we demonstrate that exogenous expression of either the SKIP region of SNW 1 or the N‐terminus region of EFTUD 2 significantly promoted cellular apoptosis. Our results suggest that the inhibition of SNW 1 or its associating proteins may be a novel therapeutic strategy for cancer treatment.