[Special Issue: Fact Databases and Freewares] RIKEN Natural Products Encyclopedia (RIKEN NPEdia),a Chemical Database of RIKEN Natural Products Depository (RIKEN NPDepo)

Tomiki, Takeshi; Saito, Tamio; Ueki, Masaaki; Konno, Hiroyuki; Asaoka, T.; Suzuki, Ryuichiro; Uramoto, Masakazu; Kakeya, Hideaki; Osada, Hiroyuki

doi:10.2751/jcac.7.157

Cited by 28 publications

(18 citation statements)

References 3 publications

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“…Purpurogallin Inhibits PBD-dependent Binding in Vitro and in Vivo-We implemented this screening system in a screen of compounds that were stored in RIKEN NPDepo (Natural Products Depository) (33). Among about 2500 compounds screened, a benzotropolone-containing natural compound derived from nutgalls PPG ( Fig.…”

Section: Development Of the Screening System For Pbd-dependentmentioning

confidence: 99%

“…In the present study we have developed a high-throughput screening system to identify small molecule inhibitors of PBD-dependent binding and implemented this assay in a screen of compounds that were stored in RIKEN NPDepo (Natural Products Depository) (33). We found several hit compounds, and one of them, purpurogallin (PPG), inhibited PBD-dependent binding in vitro and in vivo.…”

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confidence: 99%

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Deficiency in Chromosome Congression by the Inhibition of Plk1 Polo Box Domain-dependent Recognition

Watanabe

Sekine

Takagi

et al. 2009

Journal of Biological Chemistry

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106

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Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase. In eukaryotes, Plk12 (or its orthologs) possesses a wide variety of essential functions during mitosis (1, 2). Although levels of Plk1 increase in late G 2 and rapidly decrease by proteolysis at the end of M phase, Plk1 localization changes dramatically when cells transit through the various mitotic stages. During late G 2 and prophase, Plk1 localizes primarily at the centrosomes, where Plk1 is involved in centrosome maturation, separation, and microtubule nucleation (3-5). At this stage, Plk1 also regulates mitotic entry through the phosphorylation and activation of Cdc25 (6, 7). In parallel, the phosphorylation of Wee1 by Plk1, which is primed by Cdk1, promotes the destruction of Wee1, the inhibitory kinase of mitotic entry (8, 9). By metaphase, a fraction of Plk1 relocalizes to the kinetochores, where it is involved in the regulation of the spindle assembly checkpoint pathway and proper chromosome segregation. Plk1 sensitizes the tension between sister chromatids and regulates the stability of kinetochore-microtubule interactions by phosphorylating kinetochore proteins such as BubR1 and proteins that harbor 3F3/2 epitopes (4, 10 -14). Although Plk1 localization at chromosome arms is required for loss of arm cohesion during M-phase (15, 16), localized Plk1 activity at the kinetochore is important for the proper accumulation of kinetochore proteins such as BubR1, Mad1, Mad2, Cdc20, and centromere/ kinetochore-associated protein-E (CENP-E) (4, 10 -12, 17, 18). During anaphase, Plk1 is concentrated in the spindle midzone, where it may facilitate microtubule sliding. After chromosomal segregation, Plk1 remains in the central spindle and midbody, where it is involved in formation of the cleavage furrow (19 -21).These various localizations of Plk1 are mediated by its noncatalytic C-terminal half, the polo box domain (PBD), which comprises two polo box motifs (22, 23). Recently, Yaffe and co-workers (24, 25) discovered that the PBD constitutes a phosphopeptide binding domain which binds with maximal affin...

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Section: Development Of the Screening System For Pbd-dependentmentioning

confidence: 99%

mentioning

confidence: 99%

Deficiency in Chromosome Congression by the Inhibition of Plk1 Polo Box Domain-dependent Recognition

Watanabe

Sekine

Takagi

et al. 2009

Journal of Biological Chemistry

Self Cite

106

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“…Using their biology-oriented libraries, they carried out three research projects: 1) Microbiological and chemical approach for exploration of novel bioprobes, 2) Identification of molecular targets of bioprobes, 3) Mining and functional analysis of molecular targets. Besides their studies, Hiroyuki Osada also established the RIKEN Natural Products Depository (RIKEN NPDepo) to contribute to the cb/cg/cg studies by collecting biology-oriented chemical libraries [51]. They have been collecting bioprobes from natural sources worldwide, not only chemical compounds but also their physicochemical data.…”

Section: Biology-oriented Librariesmentioning

confidence: 99%

Chemical Biology/ Chemical Genetics/ Chemical Genomics: Importance of Chemical Library

文彦¹,

勝

冬彦

2007

CBIJ

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Using split-pool synthesizing methodology, small molecules produced by DOS make it possible for us to obtain compounds that span a wide chemical space. Here, we discuss cb/cg/cg studies applied to signal transduction, stem cell differentiation and small G-protein researches. All of these studies are conducted not only using biology-oriented libraries but also DOS-oriented libraries. Although cb/cg/cg is a relatively young science that aims the post-genome era sciences, it must bridge chemistry and biology not only in the academia but also in pharmaceutical industries.

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“…19) We modified their method and developed a unique, systematic ligandscreening strategy. The platform consists of a chemical array that bears compounds deposited in the Natural Product Depository (NPDepo) 20) and the protein library generated from the Gene Library of the Osada Laboratory of RIKEN for chemical array analysis (GLORIA). 21) To use GLORIA for our chemical array system, we cloned 100 genes and engineered them to express a fusion between red fluorescent protein (RFP) 22) and the protein of interest.…”

Section: Chemical Arraymentioning

confidence: 99%

[Special Issue: Fact Databases and Freewares] RIKEN Natural Products Encyclopedia (RIKEN NPEdia),a Chemical Database of RIKEN Natural Products Depository (RIKEN NPDepo)

Cited by 28 publications

References 3 publications

Deficiency in Chromosome Congression by the Inhibition of Plk1 Polo Box Domain-dependent Recognition

Deficiency in Chromosome Congression by the Inhibition of Plk1 Polo Box Domain-dependent Recognition

Chemical Biology/ Chemical Genetics/ Chemical Genomics: Importance of Chemical Library

Introduction of New Tools for Chemical Biology Research on Microbial Metabolites

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