A5101897201- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Cell death mechanisms and regulation
- Microtubule and mitosis dynamics
- Inflammatory Bowel Disease
- Genomics and Chromatin Dynamics
- Hippo pathway signaling and YAP/TAZ
- Plant Molecular Biology Research
- Cancer-related gene regulation
- Spectroscopy Techniques in Biomedical and Chemical Research
- Microscopic Colitis
- Genomic variations and chromosomal abnormalities
- Probiotics and Fermented Foods
- Toxin Mechanisms and Immunotoxins
- Congenital limb and hand anomalies
- Microbial Inactivation Methods
- Wnt/β-catenin signaling in development and cancer
- Cancer Mechanisms and Therapy
- Plant Reproductive Biology
- Systemic Lupus Erythematosus Research
- Renal and related cancers
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Cellular Mechanics and Interactions
Osaka University
2011-2024
Aichi Cancer Center
2019
Ube Frontier University
2016
Suita Municipal Hospital
2013
Microbial Chemistry Research Foundation
2013
Keio University
2007-2009
The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with proliferation has not been well established. By exploiting intravital imaging technique, we found that motility invasive properties were closely associated cycle. In vivo inoculation human colon cells bearing fluorescence ubiquitination-based cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M more motile than G1 cells. Microarray analyses showed Arhgap11a,...
Cyclin G-associated kinase (GAK), a key player in clathrin-mediated membrane trafficking, is overexpressed various cancer cells. Here, we report that GAK expression positively correlated with the Gleason score surgical specimens from prostate patients. Embryonic fibroblasts knockout mice expressing kinase-dead (KD) form of showed constitutive hyper-phosphorylation epidermal growth factor receptor (EGFR). In addition to well-known EGFR inhibitors gefitinib and erlotinib, dietary flavonoid...
Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of cell cycle, but its actual point action not clarified. Here, using time lapse imaging analyses human HCC line HuH7 carrying a fluorescence ubiquitination-based cycle indicator (Fucci), we found that induced arrest G0/G1 phases, leading apoptosis through an type-2 receptor (IFNAR2)-dependent...
Abstract Radiotherapy is a commonly used regimen for treating various types of intractable cancers, although the effects depend on cell cycle targeted cancer lines, and irradiation purposes it therefore critical to establish protocol controlling cycle. Here, we showed that common murine melanoma line B16BL6 was more vulnerable during early S phase, synchronisation greatly increased therapeutic radiotherapy. Cell-sorting experiments, according cell-cycle using cells demonstrated in phase were...
Gefitinib (Iressa) is an inhibitor of the epidermal growth factor receptor (EGFR) that has shown promising activity in treatment patients with non-small cell lung cancer (NSCLC). However, adverse side effects gefitinib treatment, such as respiratory dysfunction, have limited therapeutic benefit this targeting strategy. The present results show effect can be attributed to inhibition novel target GAK (Cyclin G-associated kinase), which potently inhibited by drug tyrosine kinase EGFR. Knockout...
Protein phosphatase 2A (PP2A) bearing the B’γ (= B’α/B56γ1/PR61γ) subunit is recruited to dephosphorylation targets by cyclin G. We demonstrate here that G-associated kinase (GAK), a component of GAK/B’γ/cyclin G complex, directly phosphorylates B’γ-Thr104 residue and regulates PP2A activity. Indeed, an anti-B’γ-pT104 antibody detected immunofluorescence signals at chromosome centrosome during mitosis; these were reduced siRNA-mediated GAK knockdown. After DNA damage γ-irradiation, formed...
Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, poorly understood. Here, we found that LATS1/2, core Hippo pathway-kinases, were highly expressed oral squamous cell carcinoma line SAS, exhibits high capacity CSCs, depletion these kinases prevented SAS from forming spheres under serum-free conditions. Detailed...
Cyclin G2 (CycG2) and G1 (CycG1), two members of the G subfamily, share high amino acid homology in their boxes. Functionally, they play a common role as association partners B′γ subunit protein phosphatase 2A (PP2A) regulate PP2A function, expression is increased following DNA damage. However, whether or not CycG1 CycG2 have distinct roles during cellular damage response has remained unclear. Here, we report that CycG2, but CycG1, co-localized with promyelocytic leukemia (PML) γH2AX,...
Abstract Cyclin G1 (CycG1) and G2 (CycG2) play similar roles during the DNA damage response (DDR), but their detailed remain elusive. To investigate distinct roles, we generated knockout mice deficient in CycG1 (G1KO) or CycG2 (G2KO), as well double (DKO) both proteins. All knockouts developed normally were fertile. Generation of mouse embryonic fibroblasts (MEFs) from these revealed that G2KO MEFs, not G1KO DKO resistant to insults caused by camptothecin ionizing radiation (IR) underwent...
Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also Y1149. An anti-GAK-pY412 antibody recognized the shifted band of during M phase. Immunofluorescence (IF) showed GAK-pY412/pY1149 signals were present in nucleus interphase, translocated to chromosomes prophase and prometaphase, moved centrosomes metaphase, finally end...
p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here TAp63 phosphorylated at T46/T281 specifically upregulates late cornified envelope 1C (LCE1C) gene is essential relatively stage of epithelial development. identified these phosphorylation sites during search for targets Cyclin G-associated kinase (GAK) in vitro....
Clathrin regulates mitotic progression, in addition to membrane trafficking. However, the detailed regulatory mechanisms of clathrin during mitosis remain elusive. Here, we demonstrate novel regulation phase cell cycle. heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation required for proper proliferation and tumor growth cells implanted into nude mice. Immunofluorescence analysis showed that localization CHC-pT606...
Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis characterization plasmablast-derived monoclonal antibodies uncovered expansion plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half expanded CL-reactive clones exhibited strong binding...
OBJECTIVES: The aims of the present study were to investigate plasma concentration endotoxin in patients with inflammatory bowel disease (IBD), effect metronidazole (MNZ) and symbiotics on that concentration, relationship IBD activity. METHODS: group comprised 26 quiescent ulcerative colitis (UC), all whom maintenance mesalazine treatment (1200− 2400 mg/day). control 15 subjects. Blood samples taken from subjects measure: routine blood chemistry, lipopolysaccharide binding protein (LBP)...
// Toshihiro Uchihashi 1, * , Kaori Ota 2, Yusuke Yabuno Shouichi Ohno 2 Kohshiro Fukushima Yoko Naito Mikihiko Kogo 1 Norikazu Yabuta ** and Hiroshi Nojima First Department of Oral Maxillofacial Surgery, Graduate School Dentistry, Osaka University, 565-0871, Japan Molecular Genetics, Research Institute for Microbial Diseases, These authors have contributed equally to this work Corresponding author cell biological experiments Correspondence to: Yabuta, email: nyabuta@biken.osaka-u.ac.jp...