A5062328926- Helicobacter pylori-related gastroenterology studies
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Eosinophilic Esophagitis
- Hippo pathway signaling and YAP/TAZ
- Toxin Mechanisms and Immunotoxins
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Wnt/β-catenin signaling in development and cancer
- Phytochemistry and biological activities of Ficus species
- Veterinary medicine and infectious diseases
- PI3K/AKT/mTOR signaling in cancer
- Biochemical and Molecular Research
- Enzyme function and inhibition
- Microbial Metabolites in Food Biotechnology
- PARP inhibition in cancer therapy
- Genomics and Phylogenetic Studies
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- Mechanisms of cancer metastasis
- Digestive system and related health
- Genomics, phytochemicals, and oxidative stress
- IL-33, ST2, and ILC Pathways
- Microtubule and mitosis dynamics
- Enzyme Structure and Function
Microbial Chemistry Research Foundation
2023-2025
The University of Tokyo
2012-2024
Japan Science and Technology Agency
2014-2016
Hokkaido University
2010-2012
Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the CagA-specific EPIYA-D segment binds to N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders magnitude greater EPIYA-C. This high-affinity binding achieved via cryptic interaction between Phe at +5 position from phosphotyrosine in and a hollow on phosphopeptide-binding floor. Also, duplication EPIYA-C CagA, which increases risk,...
Abstract Infection with cagA -positive Helicobacter pylori is critically associated the development of gastric cancer. The -encoded CagA delivered into epithelial cells via type IV secretion, where it interacts and thereby deregulates pro-oncogenic phosphatase SHP2. East Asian Western are two major species produced by H. circulating in countries rest world, respectively. SHP2 binding site CagA, termed EPIYA-C segment, variably duplicates infection carrying multiple segments a distinct risk...
ABSTRACT The acquisition of drug resistance poses a significant challenge for successful cancer treatment. Understanding the mechanisms by which evades action is crucial developing effective therapies. PARP inhibitors (PARPi) induce synthetic lethality in BRCA -deficient cells; however, these cells eventually develop PARPi resistance. Here, we demonstrate that prolonged exposure to or Cisplatin leads alterations YAP1 pre-mRNA splicing patterns, resulting selective upregulation minor isoform,...
More than 50% of people in the world are infected with Helicobacter pylori (H. pylori), which induces various gastric diseases. Especially, epidemiological studies have shown that H. infection is a major risk factor for cancer. It has been reported levels interleukin (IL)-1β upregulated tissues patients infection. In this study, we investigated induction mechanism IL-1β during We found IL-1βmRNA and protein were induced phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells after...
Abstract Chronic infection with cagA -positive Helicobacter pylori is the strongest risk factor for atrophic gastritis, peptic ulcers and gastric cancer. CagA, product of gene, a bacterial oncoprotein, which, upon delivery into epithelial cells, binds to inhibits polarity-regulating kinase, partitioning-defective 1b (PAR1b) [also known as microtubule affinity-regulating kinase 2 (MARK2)], via its CagA multimerization (CM) motif. The inhibition PAR1b elicits junctional polarity defects,...
Abstract Helicobacter pylori cagA -positive strains are critically involved in the development of gastric cancer. Upon delivery into epithelial cells via type IV secretion, -encoded CagA interacts with and thereby perturbs pro-oncogenic phosphatase SHP2 polarity-regulating kinase PAR1b tyrosine-phosphorylated EPIYA-C/D segment CM sequence, respectively. Importantly, sequences spanning these binding regions exhibit variations among proteins, which influence pathobiological/oncogenic potential...
Current X-ray sources—such as high-flux synchrotron radiation and XFEL—enable us to determine the tertiary structures of proteins at medium or low resolution even from crystals with poor quality. However, high-resolution crystal are still required obtain detailed information about protein in pharmaceutical biochemical sciences. To improve quality, several types post-crystallization treatments, including soaking experiments, have been utilized. such treatments do not always a new method...
In addition to acting as a transcriptional co-activator, YAP1 directly mediates translocalization of the pro-oncogenic phosphatase SHP2 from cytoplasm nucleus. cytoplasm, potentiates RAS–ERK signaling, which promotes cell proliferation and motility, whereas in nucleus, it gene regulation. As result, elucidating details trafficking is important for understanding its biological roles, including cancer. comprises multiple splicing isoforms defined part by presence (as YAP1-2γ) or absence...
PAR1b is a cytoplasmic serine/threonine kinase that controls cell polarity and cell–cell interaction by regulating microtubule stability while mediating cytoplasmic-to-nuclear translocation of BRCA1. also cellular target the CagA protein Helicobacter pylori, which leads to chronic infection causatively associated with development gastric cancer. The CagA-PAR1b inactivates activity thereby dampens PAR1b-mediated BRCA1 phosphorylation, reduces level nuclear BRCAness BRCAness-associated genome...
CagA is known as a major bacterial virulence determinant from Helicobacter pylori and critical for gastric cancer. Upon delivery into the epithelial cells, localizes to inner leaflet of plasma membrane promiscuously interacts with host proteins such PAR1b SHP2. The CagA-PAR1-SHP2 complex potentiates oncogenic signaling. Biochemical physicochemical analyses revealed that comprises structured N-terminal region (residues 1-876) an intrinsically disordered C-terminal 877-1186). To understand...