Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells

Naoki Sato, Masao Maeda, Mai Sugiyama, Satoko Ito, Toshinori Hyodo, Akio Masuda, Nobuyuki Tsunoda, Toshio Kokuryo, Michinari Hamaguchi, Masato Nagino, Takeshi Senga

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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 SNW1, a component of the spliceosome, induces apoptosis in breast cancer cells. Proteomics and biochemical analyses revealed that SNW1 directly associates with other spliceosome components, including EFTUD2 (Snu114) and SNRNP200 (Brr2). The SKIP region of SNW1 interacted with the N-terminus of EFTUD2 as well as two independent regions in the C-terminus of SNRNP200. Similar to SNW1 depletion, knockdown of EFTUD2 increased the numbers of apoptotic cells. Furthermore, we demonstrate that exogenous expression of either the SKIP region of SNW1 or the N-terminus region of EFTUD2 significantly promoted cellular apoptosis. Our results suggest that the inhibition of SNW1 or its associating proteins may be a novel therapeutic strategy for cancer treatment. SNW1, EFTUD2, and SNRNP200 are critical regulators for RNA splicing. SNW1 directly associates with EFTUD2 and SNRNP200, and inhibition of the SNW1 association promotes apoptosis o breast cancer cells.

本文言語English
ページ(範囲)268-277
ページ数10
ジャーナルCancer Medicine
4
2
DOI
出版ステータスPublished - 01-02-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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