A5069440644- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Cell death mechanisms and regulation
- Sleep and Wakefulness Research
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Sleep and related disorders
- Histone Deacetylase Inhibitors Research
- Blockchain Technology Applications and Security
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- FOXO transcription factor regulation
- Protease and Inhibitor Mechanisms
- Diet and metabolism studies
- Technology Adoption and User Behaviour
- Immunotherapy and Immune Responses
- Cardiac Fibrosis and Remodeling
- Privacy, Security, and Data Protection
- Fungal and yeast genetics research
Kindai University
2015-2024
Bunkyo University
2011-2022
National Institute of Informatics
2010-2019
University Health Network
2004-2017
Princess Margaret Cancer Centre
2007-2017
Jichi Medical University
2017
University of Amsterdam
2015
London Cancer
2015
University College London
2015
St. Jude Children's Research Hospital
2015
In response to ionizing radiation (IR), the tumor suppressor p53 is stabilized and promotes either cell cycle arrest or apoptosis.Chk2 activated by IR contributes this stabilization, possibly direct phosphorylation.Like p53, Chk2 mutated in patients with Li-Fraumeni syndrome.Since ataxia telangiectasia (ATM) gene required for IR-induced activation of Chk2, it has been assumed that ATM act a linear pathway leading activation.To clarify role tumorigenesis, we generated genetargeted...
The serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in cytosol, has been implicated promoting cell death by binding to inhibitor of apoptosis proteins (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase activity, and also mediating caspase-independent through own activity. We report here phenotype mice entirely lacking expression due targeted deletion gene, Prss25. These animals, or cells derived them,...
Abstract Copper plays pivotal roles in metabolic homoeostasis, but its potential role human tumorigenesis is not well defined. Here, it revealed that copper activates the phosphoinositide 3‐kinase (PI3K)‐protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, binds 3‐phosphoinositide dependent protein 1 (PDK1), turn promotes PDK1 binding and subsequently downstream substrate AKT Blocking transporter (CTR1)‐copper axis by either...
Estrogen is a key regulator of normal function female reproductive system and plays pivotal role in the development progression breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes component estrogen signaling pathway. expressed high proportion human tumors, expression levels significantly correlate with receptor (ER) positivity. In addition, 17-beta-estradiol (E2) induces an ERα dependent manner. interacts components SWI/SNF-B chromatin remodeling complex....
Forkhead box class O 3a (FOXO3a) is a transcription factor and tumor suppressor linked to longevity that determines cell fate through activating of differentiation, survival, apoptotic genes. Recruitment the coactivator CBP/p300 crucial step in transcription, we revealed addition conserved region 3 (CR3) FOXO3a, C-terminal segment CR2 (CR2C) binds contributes transcriptional activity. CR2C CR3 FOXO3a interact with KIX domain at both “MLL” “c-Myb” binding sites simultaneously. A CR2C-CR3...
The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of inhibitor proteins (IAPs). In response apoptotic stimuli, Smac is released into cytosol and promotes caspase activation binding IAPs, thereby blocking their function. These observations have suggested that a new regulator apoptosis. To better understand physiological in normal cells, we generated Smac-deficient (Smac(-/-)) mice using homologous...
Recent studies revealing that endothelial cells derived from E8.5-E10.5 mouse embryos give rise to haematopoietic appear correspond previous histological observations cell clusters are attached the ventral aspect of dorsal aorta in such a way as if they were budding layer. Gene disruption have revealed Runx1/AML1 is required for definitive haematopoiesis but not primitive haematopoiesis, precise stage gene function yet known. We found mice deficient (an alpha subunit transcription factor...
FKHRL1 (FOXO3a) and p53 are two potent stress-response regulators. Here we show that these transcription factors exhibit "crosstalk" in vivo. In response to DNA damage, activation led phosphorylation subcellular localization change, which resulted inhibition of activity. AKT was dispensable for p53-dependent suppression FKHRL1. By contrast, serum- glucocorticoid-inducible kinase 1 (SGK1) significantly induced a manner after this induction through extracellular signal-regulated 1/2-mediated...
Because survivin-null embryos die at an early embryonic stage, the role of survivin in thymocyte development is unknown. We have investigated by deleting gene only T lineage and show here that loss blocks transition from CD4− CD8− double negative (DN) thymocytes to CD4+ CD8+ positive cells. Although pre–T cell receptor signaling pathway intact survivin-deficient thymocytes, cells cannot respond its signals. In response proliferative stimuli, cycling DN exhibit cycle arrest, a spindle...
In response to DNA damage, p53 undergoes post-translational modifications (including acetylation) that are critical for its transcriptional activity. However, the mechanism by which acetylation is regulated still unclear. Here, we describe an essential role HLA-B-associated transcript 3 (Bat3)/Scythe in controlling of required damage responses. Depletion Bat3 from human and mouse cells markedly impairs p53-mediated transactivation target genes Puma p21 . Although damage-induced...
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets underlying mechanisms have remained elusive. We found that dietary induced apoptosis to remove the intestinal stem cells with nuclear or phosphorylated β-catenin APC Min/+ mice. NSAIDs also human colonic polyps removed aberrant Wnt signaling. Furthermore, deficiency SMAC, a mitochondrial apoptogenic protein, attenuated tumor-suppressive...
Fungal cytokinesis requires the assembly of a dividing septum wall. In yeast, has to be selectively digested during critical cell separation process. Fission yeast wall α(1-3)glucan is essential, but nothing known about its localization and function in or cooperation between α- β(1-3)glucan synthases Ags1 Bgs for assembly. Here, we generate physiological Ags1-GFP variant demonstrate tight colocalization with Bgs1, suggesting important early steps construction. Moreover, define essential...
Epigenetic alterations, such as histone methylation, modulate Myc signaling, a pathway central to oncogenesis. We investigated the role of demethylase KDM4B in N-Myc–mediated neuroblastoma pathogenesis. Spearman correlation was performed correlate MYCN and expression. RNA interference, microarray analysis, gene set enrichment real-time polymerase chain reaction were used define functions KDM4B. Immunoprecipitation immunofluorescence assess protein-protein interactions between N-Myc Chromatin...
Endothelial cells play an important role in maintenance of the vascular system and repair after injury. Under proinflammatory conditions, endothelial can acquire a mesenchymal phenotype by process named endothelial-to-mesenchymal transition (EndMT), which affects functional properties cells. Here, we investigated epigenetic control EndMT. We show that histone demethylase JMJD2B is induced EndMT-promoting, proinflammatory, hypoxic conditions. Silencing reduced TGF-β2-induced expression genes,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most lethal forms cancer. Although in last decade, an increase 5-year patient survival has been observed, mortality rate remains high. As a first-line treatment for PDAC, gemcitabine alone or combination (gemcitabine plus paclitaxel) used; however, drug resistance to this regimen growing issue. In our previous study, we reported MYC/glutamine dependency as therapeutic target gemcitabine-resistant PDAC secondary...
Akt is a serine-threonine kinase known to exert antiapoptotic effects through several downstream targets. cleaved during mitochondrial-mediated apoptosis in caspase-dependent manner. The reason for this not clear, however, because has been demonstrated be activated response mitochondrial apoptotic stimuli. Accordingly, we explored whether the well described stimuli staurosporine (STS) and etoposide activate such activation impacts apoptosis. Both STS NIH 3T3 cells, maximally at 8 2 h,...
The cell structure has been studied using light and electron microscopies for centuries, it is assumed that the whole clarified by now. Little quantitative three-dimensional analysis of structure, however, undertaken. We have coined a new word, 'structome', combining 'structure' '-ome', defined as 'quantitative structural information at microscopic level'. In present study, we performed structome Saccharomyces cerevisiae, one most widely researched biological materials, freeze-substitution...
Background —Ischemia with or without reperfusion induces the release of diverse products from monocytes, including cytokines such as interleukin-1 (IL-1). To determine whether these phenomena modulate fibrinolysis and potentially exacerbate impairment macrocirculation, microcirculation, both, we characterized effects IL-1 on expression fibrinolytic system matrix proteins in rat cardiac microvascular endothelial cells (CMECs). Methods Results —Confluent CMECs were exposed to serum-free medium...