A5049073157- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Chronic Lymphocytic Leukemia Research
- Mechanisms of cancer metastasis
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Chronic Myeloid Leukemia Treatments
- Biochemical and Molecular Research
- Mitochondrial Function and Pathology
- Acute Myeloid Leukemia Research
- Amino Acid Enzymes and Metabolism
- Cellular Mechanics and Interactions
- Cancer, Hypoxia, and Metabolism
- Folate and B Vitamins Research
- Metabolism, Diabetes, and Cancer
- Metal-Catalyzed Oxygenation Mechanisms
- Telomeres, Telomerase, and Senescence
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Polyamine Metabolism and Applications
- Metalloenzymes and iron-sulfur proteins
- NF-κB Signaling Pathways
National Taiwan University
2015-2024
Genomics Research Center, Academia Sinica
2020
National Yang Ming Chiao Tung University
2013-2019
Institute of Molecular Medicine
2016
Institute of Molecular Biology
2015
National Yang Ming University Hospital
2014-2015
Swedish University of Agricultural Sciences
2014
The University of Texas Health Science Center at San Antonio
1998
Chang Gung University of Science and Technology
1994-1995
Chang Gung University
1990-1994
The RhoA GTPase plays a vital role in assembly of contractile actin-myosin filaments (stress fibers) and associated focal adhesion complexes adherent monolayer cells culture. GEF-H1 is microtubule-associated guanine nucleotide exchange factor that activates upon release from microtubules. overexpression deficient microtubule binding or treatment HeLa with nocodazole to induce depolymerization results Rho-dependent actin stress fiber formation cell morphology. However, whether required...
The expression of human thymidine kinase 1 (hTK1) is highly dependent on the growth states and cell cycle stages in mammalian cells. amount hTK1 significantly increased cells during progression to S M phases, becomes barely detectable early G(1) phase by a proteolytic control mitotic exit. This tight regulation important for providing correct pool dTTP DNA synthesis at right time cycle. Here, we investigated mechanism responsible degradation hTK1. We show that degraded via...
Cell migration involves the cooperative reorganization of actin and microtubule cytoskeletons, as well turnover cell-substrate adhesions, under control Rho family GTPases. RhoA is activated at leading edge motile cells by unknown mechanisms to stress fiber assembly, contractility, focal adhesion dynamics. The microtubule-associated guanine nucleotide exchange factor (GEF)-H1 activates when released from microtubules initiate a RhoA/Rho kinase/myosin light chain signaling pathway that...
Mitochondria regulate the immune response after dengue virus (DENV) infection. Microarray analysis of genes identified upregulation mitochondrial cytidine/uridine monophosphate kinase 2 (CMPK2) by DENV We used small interfering RNA-mediated knockdown (KD) and CRISPR-Cas9 knockout (KO) approaches, to investigate role CMPK2 in mouse human cells. The results showed that was critical DENV-induced antiviral cytokine release oxidative stress DNA cytosol. activation Toll-like receptor (TLR)-9,...
Abstract NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on mitochondrial outer membrane (MOM). Here, we report role in hypoxia-induced mitophagy dependent its active site phosphohistidine but not NDPK function. Mice carrying knock-in mutation Nme3 gene disrupting histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities cerebellar Our mechanistic analysis reveals that phosphatidic acid (PA) mitochondria...
This report identifies a novel gene encoding 15-oxoprostaglandin-Delta13-reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. The expression of PGR-2 is up-regulated in late phase 3T3-L1 adipocyte differentiation and predominantly distributed adipose tissue. Overexpression cells decreases peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent transcription prohibits without affecting PPARgamma. Interestingly, we found that can...
Mitochondria are dynamic organelles regulated by fission and fusion processes. The of membranes requires elaborative coordination proteins lipids is particularly crucial for the function quality control mitochondria. Phosphatidic acid (PA) on mitochondrial outer membrane generated PLD6 facilitates However, how PA promotes remains unclear. Here, we show that a protein, NME3, required PLD6-induced tethering or clustering. NME3 enriched at contact interface two closely positioned mitochondria...
Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for new therapy against TKI-resistant CML. In vitro in vivo treatment JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable JMF4073. Evidence is presented that ATF4-mediated upregulation GSH be...
Anaphase promoting complex/cyclosome (APC/C)-mediated proteolysis is essential for chromosome segregation, mitotic exit, and G1 entry. Here, we show the importance of APC/C in control dTTP pool size mammalian cells. Two enzymes, thymidine kinase 1 (TK1) thymidylate (TMPK), involved formation are targets pathway. We demonstrate that TMPK recognized degraded by APC/C–Cdc20/Cdh1-mediated pathways from mitosis to early phase, whereas TK1 targeted degradation APC/C–Cdh1 after exit. Overexpression...
Aging of IMR-90 human diploid fibroblasts in vitro is accompanied by significant changes polyamine metabolism, most notably, a 5-fold decrease serum-induced activity ornithine decarboxylase, the key enzyme biosynthesis polyamines (Chen, K. Y., Chang, Z. F., and Liu, A. Y.-C. (1986) J. Cell. Physiol. 129, 142-146). In this paper, we employed Northern blot hybridization affinity radiolabeling techniques to investigate molecular basis age-associated change decarboxylase activity. Since...
Abstract Background Application of superparamagnetic iron oxide nanoparticles (SPIOs) as the contrast agent has improved quality magnetic resonance (MR) imaging. Low efficiency loading commercially available into cells and cytotoxicity previously formulated complexes limit their usage image probe. Here, we new cationic lipid containing SPIOs feasible for in vivo Methods Hydrophobic were incorporated 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP)...
Significance It is known that nutrient starvation stimulates mitochondrial fusion for cell survival. In this study, a homozygous mutation in the NME3 gene, which encodes an NDP kinase, was identified fatal neurodegenerative disorder. Cells derived from patient were deficient of and intolerant to glucose starvation. Patient cells used demonstrate rescued survival by two separate functions, namely stimulation kinase activity. Since dynamics energy efficiency are important neuronal development,...
The nuclear protein interacting with the distal CCAAT box of human thymidine kinase (TK) gene promoter has been suggested to be a specific TK-CCAAT-binding protein, which is responsible for serum-dependence TK transactivation in normal IMR-90 fibroblasts. By biochemical characterization, was found distinct from other known CCAAT-binding proteins (Pang, J. H., and Chen, K. Y. (1993) Biol. Chem. 268, 2909-2916). In this study, we identify NF-Y, composed Ya Yb subunits, TK-CCAAT binding...
Focal adhesions (FAs) undergo maturation that culminates in size and composition changes modulate adhesion, cytoskeleton remodeling differentiation. Although it is well recognized stimuli for osteogenesis of mesenchymal stem cells (MSCs) drive FA maturation, actin organization stress fiber polarization, the extent to which FA-mediated signals regulated by protein specifies MSC commitment remains largely unknown. Here, we demonstrate that, upon dexamethasone (osteogenic induction) treatment,...
Abstract We have previously shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a major role in growth zone chondrocyte (GC) differentiation and this effect is mediated by protein kinase C (PKC). The aim of the present study was to identify signal transduction pathway used 1,25(OH)2D3 stimulate PKC activation. Confluent, fourth passage GC cells from costochondral cartilage were evaluate mechanism Treatment cultures with elicited dose-dependent increase both inositol-1,4,5-trisphosphate...
Introduction: Functional and structural changes of atrial tissue occur during the natural course fibrillation (AF), these may contribute to further AF. We investigated in AF using cDNA microarray two‐dimensional protein electrophoresis techniques. Methods Results: established a porcine model by rapid right appendage pacing at rate 600/min. Atrial was obtained after depolarization for 6 weeks. Microarrays containing 6,035 clones were used evaluate alterations mRNA. Two‐dimensional performed...
The expression of cytosolic human thymidine kinase (TK) occurs in a cell cycle-dependent manner. Here, we show that TK is hyperphosphorylated during the M phase several lines. Our data from characterizing phosphorylation proliferating and phase-arrested HeLa cells suggest polypeptide differentially phosphorylated progression cycle. was found to have 10-fold lower affinity for its substrate, thymidine, than cells. We propose by mitotic kinase(s) may provide an attenuating mechanism prevent...
In response to treatment with phorbol-12-myristate-13-acetate (PMA), the half-population of erythromyeloblast D2 cells, a cytokine-independent variant TF-1 displayed adhesion and differentiated into monocyte/macrophage-like morphology, while other remained in suspension underwent apoptosis. Expression cell cycle inhibitor p21(Cip1/Waf1) was induced after PMA adherent cells but not proapoptotic cells. We investigated mechanism responsible for impairment induction PMA-induced demonstrated that...
The induction of Bcl-x L is critical for the survival late proerythroblasts.The erythroid-specific transcriptional network that regulates expression in erythropoiesis remains unclear.The activation central erythropoietic factor, GATA-1, leads to early, transient a transcription repressor, Gfi-1B, followed by during erythroid maturation G1ER cells.Chromatin immunoprecipitation assays demonstrated constant level GATA-1 binds promoter throughout entire period, while Gfi-1B transiently...
// Ting-Yun Chuang 1 , An-Jie Cheng I-Ting Chen Tien-Yun Lan I-Hsuan Huang Chung-Wai Shiau 2 Chia-Lin Hsu 3 Ya-Wen Liu 4 Zee-Fen Chang Ping-Hui Tseng and Jean-Cheng Kuo 1, 5, 6 Institute of Biochemistry Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan Biopharmaceutical Sciences, Microbiology Immunology, Medicine, College 10002, 5 Biophotonics & Imaging Research Center, Proteomics Correspondence to: Kuo, email: jckuo@ym.edu.tw Keywords: TNF-α secretion, dexamethasone,...
Abstract This study used DNA methyltransferase 3b (DNMT3b) knockout cells and the functional loss of DNMT3b mutation in immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) to understand how dysfunction causes genome instability. We demonstrated that R-loops contribute damages ICF cells. More prominent damage signal was due expression acquirement p53 mutation. Genome-wide ChIP-sequencing mapped sites at satellite repetitive sequences including (peri-)centromere regions....
Prior studies have shown that 24,25-(OH)2D3 and 1,25-(OH)2D3 regulate protein kinase C (PKC) in costochondral chondrocytes a cell maturation-dependent manner, with affecting primarily growth zone (GC) cells resting (RC) cells. In addition, has been to increase phospholipase A2 activity GC, while decrease RC. Stimulation of GC caused an PKC, whereas inhibition RC cultures increased both basal 24,25-(OH)2D3-induced PKC activity, suggesting may play central role mediating the effects vitamin D...