Yoshie Noguchi

Daiichi Sankyo Company, Tokyo, Tokyo-to, Japan

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Publications (3)9.75 Total impact

  • Takeyuki Sugiura, Yoshie Noguchi
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    ABSTRACT: Protein phosphatase 2C (PP2C) family is characterized by requirement of metal cation for phosphatase activity. We previously established that PPM1H is a cancer-associated member of the PP2C family. Here we further characterized the phosphatase activity of PPM1H, focusing on its dependence on metal cation. PPM1H possesses the potential to dephosphorylate p-nitrophenyl phosphate (pNPP), casein and phosphopeptides. Interestingly, PPM1H shows the metal preference that is varied depending on the substrate (substrate-dependent metal preference); PPM1H prefers Mn(2+) when pNPP or phosphopeptides is used as a substrate. Meanwhile, a preference for Mg(2+) is displayed by PPM1H with casein as a substrate. When both cations are added to the reaction, the degree of the effect is always closer to that with Mn(2+) alone, irrespective of the substrate. This preponderance of Mn(2+) is explained by its greater affinity for PPM1H than Mg(2+). From the literature the substrate-dependent metal preference appears to be shared by other PP2Cs. According to the crystal structure, a binuclear metal center of PP2C plays an important role for coordinating the substrate and nucleophilic waters in the active site. Therefore, the differences in the size, preferred geometry and coordination requirements between two metals, in relation to the substrate, may be responsible for this intriguing property.
    Biology of Metals 04/2009; 22(3):469-77. · 3.17 Impact Factor
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    ABSTRACT: In search for a new anticancer drug target, we explored genes involved in colon adenocarcinoma development through dysregulation of a signal transduction pathway. By using the gene expression profile database, we found protein phosphatase 1H (PPM1H), belonging to the protein phosphatase 2C (PP2C) family, upregulated in colon adenocarcinomas compared with normal colon tissues. RT-PCR analysis verified the elevated level of PPM1H expression in colon cancer cell lines relative to a normal colon cell line. PPM1H encodes a protein with a molecular mass of approximately 50 kDa that resides in the cytoplasm. PPM1H fused with maltose-binding protein expressed in E. coli exhibited phosphatase activity characteristic of the PP2C family. Co-immunoprecipitation coupled with mass spectrometry analysis identified CSE1L, a proliferation and apoptosis-related protein, as a PPM1H-interacting protein. Native, but not inactive, PPM1H expressed in HeLa cells increased the mobility of CSE1L on SDS gels and a similar mobility shift was observed for purified CSE1L after treatment with PPM1H in vitro, supporting the notion that CSE1L is a substrate of PPM1H. Dominant negative PPM1H protected HeLa cells from cell death triggered by staurosporine or taxol. Additionally, knockdown of PPM1H expression with small interfering RNAs suppressed the growth of MCF-7 cells weakly but consistently. PPM1H controls cell cycle and proliferation of cancer cells potentially through dephosphorylation of CSE1L and might be a new target of anticancer drugs.
    Cancer biology & therapy 03/2008; 7(2):285-92. · 3.29 Impact Factor
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    Takeyuki Sugiura, Yuki Nagano, Yoshie Noguchi
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    ABSTRACT: To explore differentially expressed genes involved in non-small cell lung cancer progression, we used the gene expression profile database of various human tissues and identified DDX39, a new member of the DEAD box RNA helicases, showing overexpression in human lung squamous cell carcinoma (LSCC) but not in lung adenocarcinoma (LAC). There existed three types of alternatively spliced DDX39 variants (DDX39-L, -S and -SS), of which only DDX39-L contains all the motifs required for RNA helicase activity. RT-PCR analysis verified the increased expression of DDX39-L in LSCC, but not LAC, cultured cells compared with normal bronchial epithelial cells. A high sequence similarity to UAP56 and punctate nuclear localization pattern of DDX39-L suggest that it plays a role in RNA splicing/export. Recombinant DDX39-L binds RNA, hydrolyzes NTPs in an RNA-dependent manner and unwinds double strand RNA bidirectionally, proving that DDX39 is an RNA helicase. Overexpression of DDX39-L stimulates colony formation of HeLa cells, probably through elevation of a translational level, indicating the biological significance of DDX39 in cancer pathogenesis. Thus, DDX39 is a novel RNA helicase capable of promoting cancer cell growth and, thereby, can be a potential target for development of a therapeutic strategy for LSCC.
    Cancer biology & therapy 07/2007; 6(6):957-64. · 3.29 Impact Factor

Publication Stats

34 Citations
9.75 Total Impact Points

Institutions

  • 2007–2009
    • Daiichi Sankyo Company
      • Lead Discovery Research Laboratories
      Tokyo, Tokyo-to, Japan