title: Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells.
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.
authors.affiliation: Department of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.forename: Mai
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.forename: Akio
authors.initials: A
authors.lastname: Masuda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.forename: Toshio
authors.initials: T
authors.lastname: Kokuryo
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D056918:Nuclear Receptor Coactivators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism
chemical_list: C581608:EFTUD2 protein, human; D056918:Nuclear Receptor Coactivators; D010445:Peptide Elongation Factors; D017415:Ribonucleoprotein, U5 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C545711:SNRNP200 protein, human; C111791:SNW1 protein, human
keywords: Apoptosis; EFTUD2; PRPF8; RNA splicing; SNRNP200; SNW1