A5000708721- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Microbial Natural Products and Biosynthesis
- Photosynthetic Processes and Mechanisms
- Cancer-related Molecular Pathways
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- PI3K/AKT/mTOR signaling in cancer
- 14-3-3 protein interactions
- Melanoma and MAPK Pathways
- Chemical Synthesis and Analysis
- Plant biochemistry and biosynthesis
- Microtubule and mitosis dynamics
- Cell death mechanisms and regulation
- Bioactive Compounds and Antitumor Agents
- Hops Chemistry and Applications
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Cancer Cells and Metastasis
- RNA regulation and disease
- Hippo pathway signaling and YAP/TAZ
- Microbial Metabolism and Applications
- Heat shock proteins research
Showa Pharmaceutical University
2021-2024
Keio University
2015-2024
RIKEN Advanced Science Institute
2012
Kyoto Institute of Technology
2011
RIKEN
2007
The IRE1α-XBP1 pathway, a key component of the endoplasmic reticulum (ER) stress response, is considered to be critical regulator for survival multiple myeloma (MM) cells. Therefore, availability small-molecule inhibitors targeting this pathway would offer new chemotherapeutic strategy MM. Here, we screened ER stress-induced XBP1 activation, and identified toyocamycin from culture broth an Actinomycete strain. Toyocamycin was shown suppress thapsigargin-, tunicamycin- 2-deoxyglucose-induced...
Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, precise mechanism antitumour effects XN on (E2)-dependent cell growth and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus whether directly binds to tumour suppressor protein prohibitin 2 (PHB2), forming novel targeting BIG3-PHB2 complex acting as pivotal modulator E2/ERα signalling in treatment effectively...
Autophagy is a bulk, nonspecific protein degradation pathway that involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed xanthohumol (XN), prenylated chalcone present hops (Humulus lupulus L.) beer, modulates autophagy. By using XN-immobilized beads, valosin-containing (VCP) was identified as XN-binding protein. VCP has been reported to be an essential for autophagosome maturation. Using vitro pull down assay, showed XN bound directly N domain, which known...
Anti-apoptotic oncoproteins Bcl-2 and Bcl-xL are overexpressed in many cancers play a crucial role cancer initiation, progression, resistance to chemotherapy. Therefore, the discovery of functional inhibitor for these proteins improved understanding molecular mechanisms will be an aid novel anti-tumor therapies. Here, using chemical−genetic cell-based screening, we have discovered chemically biologically unique substance, incednine, as modulator Bcl-2/Bcl-xL from fermentation broth...
The anti-apoptotic oncoproteins Bcl-2 and Bcl-xL play crucial roles in tumorigenesis chemoresistance, are thus therapeutic cancer targets. We searched for small molecules that disturbed the function of or Bcl-xL, found vacuolar H(+)-ATPase (V-ATPase) inhibitors, such as bafilomycin A1 (BMA), showed activity. Bcl-xL-overexpressing Ms-1 cells displayed resistance to anticancer drugs, but underwent apoptosis following treatment with a combination V-ATPase inhibitors at doses similar those...
Endoplasmic reticulum (ER) stress, due to an accumulation of unfolded proteins in the ER, leads a process known as protein response (UPR). Since several compounds used induce UPR have different modes action, their mechanisms are thought be different, but it is unclear whether these can upregulate target genes with similar kinetics. Hence, we sought compare expression patterns nine induced by seven UPR-inducing compounds. Hierarchical clustering analysis revealed that were classified into two...
Gambogic acid (GA) was extracted from the dried yellow resin of gamboge (Garcinia hanburyi) which is traditionally used as a coloring material for painting and cloth dying. Gamboge has been also folk medicine an internal purgative externally infected wound. We focused on mechanisms apoptosis induction by GA through unfold protein response (ER stress) in HeLa cells.The cytotoxic effect against cells determined trypan blue exclusion assay. Markers ER stress such XBP-1, GRP78, CHOP, GADD34...
Cell migration is an essential step for tumor metastasis. The small GTPase Rac1 plays important role in cell migration. Previously, we reported that epidermal growth factor (EGF) induced two waves of activation; namely, at 5 min and 12 h after stimulation. A second wave EGF-induced activation was required migration, however, the spatiotemporal regulation remains largely unclear. In this study, found 5-lipoxygenase (5-LOX) activated process leukotriene C4 (LTC4 ) produced by 5-LOX mediated...
Macroautophagy/autophagy plays a critical role in the pathogenesis of various human diseases including neurodegenerative disorders such as Parkinson disease (PD) and Huntington (HD). Chemical autophagy inducers are expected to serve disease-modifying agents by eliminating cytotoxic/damaged proteins. Although many have been identified, their precise molecular mechanisms not fully understood because complicated crosstalk among signaling pathways. To address this issue, we performed several...
Liquid–liquid phase separation (LLPS) and the subsequent liquid–solid transition are thought to be common aggregation mechanisms of neurodegeneration-associated proteins. α-Synuclein (α-syn), whose represents major pathological hallmark Parkinson's disease, is reported undergo LLPS, which accelerates oligomer aggregate formation in vitro vivo; however, precise molecular events involved early stages α-syn remain controversial. In present study, was promoted by liquid droplets formed...
In Alzheimer disease (AD), the microtubule-associated protein tau is found hyperphosphorylated in paired helical filaments. Among many phosphorylated sites tau, Ser-262 major site for abnormal phosphorylation of AD brain. The kinase known to phosphorylate this particular MARK2, whose activation mechanism yet be studied. Our first finding that treatment cells with LiCl, a selective inhibitor another kinase, glycogen synthase kinase-3beta (GSK-3beta), inhibits led us investigate possible...
Immense previous efforts have elucidated the core machinery in cell migration, actin remodeling regulated by Rho family small GTPases including RhoA, Cdc42, and Rac1; however, spatiotemporal regulation of these molecules remains largely unknown. Here, we report that EGF induces biphasic Rac1 activation process UTKO1, a migration inhibitor, inhibits second EGF-induced wave but not first wave. To address mechanism role activation, identified 14-3-3ζ as target protein UTKO1 also showed...
In the course of screening for anti-Parkinsonian drugs from a library traditional herbal medicines, we found that extracts choi-joki-to and daio-kanzo-to protected cells MPP+-induced cell death. Because commonly contain genus Glycyrrhiza, isolated licopyranocoumarin (LPC) glycyrurol (GCR) as potent neuroprotective principals Glycyrrhiza. LPC GCR markedly blocked neuronal PC12D death disappearance mitochondrial membrane potential, which were mediated by JNK. inhibited JNK activation through...
Abstract Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles many kinds cancer different tissues. Inhibition the Ras‐depalmitoylating enzyme acyl protein thioesterases APT1 ‐2 is a new approach to modulating cycle. Here we present boronic borinic acid derivatives as class potent nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays turned out inhibit human competitive mode. Furthermore,...
Nonthmicin (1), a new polyether polyketide bearing chlorinated tetronic acid, was isolated from the culture extract of soil-derived Actinomadura strain. The structure 1 elucidated by interpretation NMR and MS spectroscopic data, absolute configuration proposed on basis crystal its dechloro congener ecteinamycin (2) also same Tetronic acids modified halogenation have never been reported natural products. Compounds 2 were found to neuroprotective activity antimetastatic properties at...
Caldorazole (1) was isolated from the marine cyanobacterium Caldora sp. collected on Ishigaki Island, Okinawa, Japan. Its structure determined to be a new polyketide that contained two thiazole rings and an O-methylenolpyruvamide moiety. showed strong cytotoxicity toward tumor cells had been seeded at high density. Cell death induced by 1 in HeLa A431 also observed only presence of glycolysis blocker 2-deoxy-d-glucose (2DG). Co-treatment with 2DG remarkably decreased ATP levels these cells....