A5049312872- RNA modifications and cancer
- Cancer-related gene regulation
- Natural product bioactivities and synthesis
- Plant biochemistry and biosynthesis
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Advances in Cucurbitaceae Research
- Computational Drug Discovery Methods
- ATP Synthase and ATPases Research
- Genomics and Chromatin Dynamics
- Plant Gene Expression Analysis
- Hemoglobinopathies and Related Disorders
- Systemic Lupus Erythematosus Research
- Phagocytosis and Immune Regulation
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Click Chemistry and Applications
- Sphingolipid Metabolism and Signaling
- Marine Sponges and Natural Products
- Chromatin Remodeling and Cancer
- Wnt/β-catenin signaling in development and cancer
- Fibroblast Growth Factor Research
- Cancer Mechanisms and Therapy
- Hippo pathway signaling and YAP/TAZ
- Cancer, Hypoxia, and Metabolism
Tokyo University of Pharmacy and Life Sciences
2022-2024
RIKEN Center for Sustainable Resource Science
2017-2023
Meiji University
2015-2021
ID Genomics (United States)
2017
Kawasaki Hospital
2015
Abstract Sickle cell disease (SCD) is a heritable disorder caused by β-globin gene mutations. Induction of fetal γ-globin an established therapeutic strategy. Recently, epigenetic modulators, including G9a inhibitors, have been proposed as agents. However, the molecular mechanisms whereby these small molecules reactivate remain unclear. Here we report development highly selective and non-genotoxic inhibitor, RK-701. RK-701 treatment induces globin expression both in human erythroid cells...
Identification of structurally novel inhibitors lysine methyltransferase G9a has been a subject intense research in cancer epigenetics. Starting with the high-throughput screening (HTS) hit rac-10a obtained from chemical library University Tokyo Drug Discovery Initiative, structure–activity relationship unique substrate-competitive was established help X-ray crystallography and fragment molecular orbital (FMO) calculations for ligand–protein interaction. Further optimization vitro...
Abstract SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex, is causative gene rhabdoid tumors and epithelioid sarcomas. Here, we identify paralog pair CBP p300 as synthetic lethal target in SMARCB1-deficient cancers by using dual siRNA screening method based on “simultaneous inhibition pair” concept. Treatment with CBP/p300 inhibitors suppresses growth cell lines tumor xenografts derived from cells but not SMARCB1-proficient cells. SMARCB1-containing complexes localize H3K27me3...
Abstract Genome-wide RNA interference (RNAi) with pooled and barcoded short-hairpin (shRNA) libraries provides a powerful tool for identifying cellular components that are relevant to the modes/mechanisms of action (MoA) bioactive compounds. shRNAs affect sensitivity given compound can be identified by deep sequencing shRNA-specific barcodes. We used multiplex barcode technology adding sample-specific index tags PCR primers during sequence library preparation, enabling parallel analysis...
Thioviridamide, prethioviridamide, and JBIR-140, which are ribosomally synthesized post-translationally modified peptides (RiPPs) possessing five thioamide bonds, induce selective apoptosis in various cancer cells, especially those expressing the adenovirus oncogene E1A. However, target protein of this unique family bioactive compounds was previously unknown. To investigate mechanism action, we adopted a combined approach genome-wide shRNA library screening, transcriptome profiling,...
Glioma amplified sequence 41 (GAS41), which has the Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain that recognizes lysine acetylation (Kac), regulates gene expression as a subunit of SRCAP (SNF2-related CREBBP activator protein) complex deposits histone H2A.Z at promoters in eukaryotes. The YEATS domains proteins AF9 ENL recognize Kac by hydrogen bonding aromatic cage to arginine situated just before K9ac or K27ac N-terminal tail H3. Curiously, GAS41 binds most preferentially contains K14ac...
Cucurbitacins are highly oxygenated triterpenoids characteristic of plants in the family Cucurbitaceae and responsible for bitter taste these plants. Fruits melon (
Cucurbitaceae plants contain characteristic triterpenoids. Momordica charantia, known as a bitter melon, contains cucurbitacins and multiflorane type triterpenes, which confer tasting exhibit pharmacological activities. Their carbon skeletons are biosynthesized from 2,3-oxidosqualene by responsible oxidosqualene cyclase (OSC). In order to identify OSCs in M. RNA-seq analysis was carried out ten different tissues. The functional of the resulting four OSC genes revealed that they were...
Critical residues controlling the 1,2-rearrangement process during cycloartenol and cucurbitadienol formation in oxidosqualene cyclase were identified.
To meet cellular bioenergetic and biosynthetic demands, cancer cells remodel their metabolism to increase glycolytic flux, a phenomenon known as the Warburg effect believed contribute malignancy. Among enzymes, phosphofructokinase-1 (PFK1) has been shown act rate-limiting enzyme facilitate in cells. In this study, however, we found that decreased PFK1 activity did not affect cell survival or proliferation This raised question regarding importance of gain insights into role possibility...
TEAD is a transcription factor responsible for the output of tumor suppressor Hippo pathway. The transcriptional activity requires molecular interaction with its coactivator, YAP. Aberrant activation deeply involved in tumorigenesis and associated poor prognosis, suggesting that inhibitors targeting YAP-TEAD system are promising as antitumor agents. In this study, we identified NPD689, an analog natural product alkaloid emetine, inhibitor interaction. NPD689 suppressed reduced viability...
<title>Abstract</title> The chromodomain protein CBX2 binds directly to histone H3 trimethylation at lysine 27 (H3K27me3) and is a component of polycomb repressive complex 1 (PRC1). plays pivotal role in transcriptional repression by acting as reader that recognizes H3K27me3. In this study, we performed <italic>in silico</italic> screening based on the crystal structure identify small molecule compounds target CBX2. ability selected inhibit interaction between cells was validated. After...
Aminoacyl-tRNA synthetases (aaRSs) play essential roles in protein translation. In addition, numerous aaRSs (mostly vertebrates) have also been discovered to possess a range of non-canonical functions. Very few studies conducted elucidate or characterize functions plant aaRSs. A genome-wide search for aaRS genes Arabidopsis thaliana revealed total 59 genes. Among them, asparaginyl-tRNA synthetase (AsnRS) was found WHEP domain inserted into the catalytic plant-specific manner. This insertion...
Abstract Imperata cylindrica is known to produce a pair of triterpenes, isoarborinol and fernenol, that exhibit identical planar structures but possess opposite stereochemistry at six the nine chiral centers. These differences arise from boat or chair cyclization B‐ring substrate. Herein, we report characterization three OSC genes I. . IcOSC1 IcOSC5 were identified as fernenol synthases, respectively, while IcOSC3 was characterized multifunctional enzyme produces glutinol friedelin its major...