A5031272334- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Synthetic Organic Chemistry Methods
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Fungal Biology and Applications
- Carbohydrate Chemistry and Synthesis
- Endoplasmic Reticulum Stress and Disease
- Chemical Synthesis and Analysis
- Plant biochemistry and biosynthesis
- ATP Synthase and ATPases Research
- Genomics and Phylogenetic Studies
- Alkaloids: synthesis and pharmacology
- Mitochondrial Function and Pathology
- Natural product bioactivities and synthesis
- Cancer therapeutics and mechanisms
- Mechanisms of cancer metastasis
- Microbial Metabolism and Applications
- Bioactive Compounds and Antitumor Agents
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
National Institute of Advanced Industrial Science and Technology
2015-2024
Japan Biological Informatics Consortium
2008-2022
The University of Tokyo
2005-2022
Tokyo Metropolitan Industrial Technology Research Institute
2021
Tohoku University
2010-2015
Koto Hospital
2015
Kyoto University
2015
Japanese Foundation For Cancer Research
2012
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2012
National Institute of Information and Communications Technology
2008-2011
Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be very potent telomerase inhibitor. The structural similarity between telomestatin G-tetrad suggested us that the inhibition might due its ability either facilitate formation of or trap out preformed G-quadruplex structures, thereby sequester single-stranded d[T2AG3]n primer molecules required for activity. Significantly, appears more inhibitor (5 nM) than any previously described...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTelomestatin, a Novel Telomerase Inhibitor from Streptomyces anulatusKazuo Shin-ya, Konstanty Wierzba, Ken-ichi Matsuo, Toshio Ohtani, Yuji Yamada, Kazuo Furihata, Yoichi Hayakawa, and Haruo SetoView Author Information Institute of Molecular Cellular Biosciences The University Tokyo Bunkyo-ku, 113-0032, Japan Graduate School Agricultural Life Sciences 113-8657, Cite this: J. Am. Chem. Soc. 2001, 123, 6, 1262–1263Publication Date (Web):January...
Significance Terpenes are generally considered to be plant or fungal metabolites, although a small number of odoriferous terpenes bacterial origin have been known for many years. Recently, extensive genome sequencing and bioinformatic analysis deduced proteins using profile based on hidden Markov model revealed 262 distinct predicted terpene synthases. Although these presumptive synthase genes seem silent in their parent microorganisms, controlled expression an engineered heterologous...
FANCJ mutations are associated with breast cancer and genetically linked to the bone marrow disease Fanconi anemia (FA). The genomic instability of FA-J mutant cells suggests that helicase functions in replicational stress response. A putative sequence similarity Caenorhabditis elegans (DOG-1) mouse (RTEL) is required for poly(G) tract maintenance, suggesting its involvement resolution alternate DNA structures impede replication. Under physiological conditions, guanine-rich sequences...
An industrial microorganism, Streptomyces avermitilis, which is a producer of anthelmintic macrocyclic lactones, avermectins, has been constructed as versatile model host for heterologous expression genes encoding secondary metabolite biosynthesis. Twenty the entire biosynthetic gene clusters metabolites were successively cloned and introduced into S. avermitilis SUKA17 or 22. Almost all transformants carrying cluster produced result introduced. A few unable to produce metabolites, but their...
Cationic porphyrins are known to bind and stabilize different types of G-quadruplexes. Recent studies have shown the biological relevance intramolecular parallel G-quadruplex as a transcriptional silencer in c-MYC promoter. TMPyP4 also binds this most likely converts it mixed parallel/antiparallel with two external lateral loops one internal propeller loop, suppressing activation. To achieve therapeutic selectivity by targeting G-quadruplexes, is necessary synthesize drugs that can...
Quadruplex ligands are often considered as telomerase inhibitors. Given the fact that some of these molecules present in clinical setting, it is important to establish validity this assertion. To analyze effects compounds, we used a direct assay with telomerase-enriched extracts. The comparison potent from various chemical families revealed differences terms on initiation and processivity. Although most quadruplex may lock quadruplex-prone sequence into structure inhibits elongation by...
Background: Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR), stress-signaling pathway, in tumor cells. We recently isolated novel macrocyclic compound, versipelostatin (VST), that inhibits transcription from promoter GRP78, gene is activated as part UPR. examined effect VST on UPR induced by glucose deprivation or other stressors and growth vivo. Methods: Human colon cancer HT-29, fibrosarcoma HT1080, stomach MKN74 cells were...
Telomestatin is a potent G-quadruplex ligand that interacts with the 3′ telomeric overhang, leading to its degradation, and induces delayed senescence apoptosis of cancer cells. POT1 TRF2 were recently identified as specific telomere-binding proteins involved in telomere capping t-loop maintenance whose interaction telomeres modulated by telomestatin. We show here treatment HT1080 human tumor cells telomestatin rapid decrease G-overhang double-stranded repeats. also provokes strong from...
Abstract Telomestatin is a potent G-quadruplex ligand that specifically interacts with the 3′ telomeric overhang, leading to its degradation and induces delayed senescence apoptosis of cancer cells. Protection Telomere 1 (POT1) was recently identified as specific single-stranded telomere-binding protein involved in telomere capping T-loop maintenance. We showed here telomestatin treatment inhibits POT1 binding overhang vitro. The human EcR293 cells by dramatic rapid delocalization from...
Significance Patients with intrahepatic cholangiocellular carcinoma (ICC) and combined hepatocellular cholangiocarcinoma (cHC-CC) have worse prognoses than those rarely show clinical responses to drugs. Our analyses of mice liver-specific deletions Mps One Binder Kinase Activator (MOB)1A/1B reveal that MOB1A/1B constitute the most important hub Hippo signaling in mammalian liver. maintain hepatocyte stem/progenitor cell quiescence are potent tumor suppressors, especially cHC-CCs ICCs....
A planar trimeric macrocyclic oligoamide of 8-amino-2-quinoline carboxylic acid, bearing ammonium side chains, stabilizes the human telomeric G-quadruplex more strongly than potent ligand telomestatin. Furthermore, a helical tetramer also binds to G-quadruplexes and is new structural class quadruplex that appears interact enantioselectively.
Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of UPR is transcription program activation, which allows to survive under stress conditions. Here, we show disrupted by antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production activators XBP1 ATF4 induce massive death during deprivation as did antitumor macrocyclic compound...
Ustiloxin B is a secondary metabolite known to be produced by Ustilaginoidea virens. In our previous paper, we observed the production of this compound Aspergillus flavus, and identified two A. flavus genes responsible for ustiloxin biosynthesis (Umemura et al., 2013). The cyclic tetrapeptide Tyr-Ala-Ile-Gly, whose tyrosine modified with non-protein coding amino acid, norvaline. Although its chemical structure strongly suggested that biosynthesized non-ribosomal peptide synthetase, in...
G-quadruplex (G4) DNA, an alternate structure formed by Hoogsteen hydrogen bonds between guanines in G-rich sequences, threatens genomic stability perturbing normal DNA transactions including replication, repair, and transcription. A variety of G4 topologies (intra- intermolecular) can form vitro, but the molecular architecture cellular factors influencing landscape vivo are not clear. Helicases that unwind structured molecules emerging as important class G4-resolving enzymes. The...
Abstract Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding gene cluster evolution provides a rationale for reprogramming the biosynthetic machinery. Herein, we report characterization giant modular polyketide synthases (PKSs) responsible production aminopolyol polyketides. Heterologous expression over 150 kbp clusters successfully afforded products, whose stereochemistry was established by taking...
Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres pericentromeric heterochromatin, which is exacerbated by loss of p53 linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence telomere fusions increased sensitivity replication stress–inducing drugs. Treatment G-quadruplex (G4) ligand telomestatin DNA damage, indicating...
Abstract Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM is largely limited to the surgically resectable tumor core lesion while seeds for recurrence reside unresectable edge. In this study, stratification and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models that retain their identity a cell autonomous manner. Upon xenotransplantation, edge-derived cells show higher...
Benzastatins have unique structures probably derived from geranylated p-aminobenzoic acids. The indoline and tetrahydroquinoline scaffolds are presumably formed by cyclization of the geranyl moiety, but mechanism was unknown. We studied benzastatin biosynthetic gene cluster Streptomyces sp. RI18; functions six enzymes encoded it were analyzed disruption in a heterologous host vitro enzyme assays. propose pathway for benzastatins which cytochrome P450 (BezE) is responsible...