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Cancer Med. 2015 Feb;4(2):268-77. doi: 10.1002/cam4.366. Epub 2014 Dec 1.

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

Author information

1
Department of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.

Abstract

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.

KEYWORDS:

Apoptosis; EFTUD2; PRPF8; RNA splicing; SNRNP200; SNW1

PMID:
25450007
PMCID:
PMC4329010
DOI:
10.1002/cam4.366
[Indexed for MEDLINE]
Free PMC Article

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