title: Four nucleocytoplasmic-shuttling proteins and p53 interact specifically with the YB-NLS and are involved in anticancer reagent-induced nuclear localization of YB-1.
abstract: In cancer cells, anticancer reagents often trigger nuclear accumulation of YB-1, which participates in the progression of cancer malignancy. YB-1 has a non-canonical nuclear localization signal (YB-NLS). Here we found that four nucleocytoplasmic-shuttling RNA-binding proteins and p53 interact specifically with the YB-NLS and co-accumulate with YB-1 in the nucleus of actinomycin D-treated cells. To elucidate the roles of these YB-NLS-binding proteins, we performed a dominant-negative experiment in which a large excess of YB-NLS interacts with the YB-NLS-binding proteins, and showed inhibitory effects on actinomycin D-induced nuclear transport of endogenous YB-1 and subsequent MDR1 gene expression. Furthermore, the YB-NLS-expressing cells were also found to show increased drug sensitivity. Our results suggest that these YB-NLS-associating proteins are key factors for nuclear translocation/accumulation of YB-1 in cancer cells.
authors: Department of Biochemistry, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors: Toru
authors: T
authors: Tanaka
authors: Department of Biochemistry, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba, 274-8555, Japan.
authors: Sachiyo
authors: S
authors: Ohashi
authors: Department of Biochemistry, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba, 274-8555, Japan. Electronic address: kobayashi.shunsuke@nihon-u.ac.jp.
authors: Shunsuke
authors: S
authors: Kobayashi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D050505:Mutant Proteins; D019913:Nuclear Localization Signals; D029543:Nucleocytoplasmic Transport Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D051840:Y-Box-Binding Protein 1; D049452:Green Fluorescent Proteins; D003609:Dactinomycin
keywords: MDR1 expression; Nuclear transport; Nucleocytoplasmic-shuttling proteins; YB-1; YB-NLS-binding proteins