A5101684789- Biochemical and Molecular Research
- Chronic Myeloid Leukemia Treatments
- Biochemical Acid Research Studies
- Genetics and Neurodevelopmental Disorders
- Antifungal resistance and susceptibility
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Chronic Lymphocytic Leukemia Research
- Mechanisms of cancer metastasis
- Natural product bioactivities and synthesis
- Biological Activity of Diterpenoids and Biflavonoids
- Phytochemistry and Biological Activities
- Metabolomics and Mass Spectrometry Studies
- Aquaculture Nutrition and Growth
- Chemical Reactions and Isotopes
- Congenital heart defects research
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Colorectal Cancer Treatments and Studies
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- Plant biochemistry and biosynthesis
- Physiological and biochemical adaptations
- Fungal Biology and Applications
- Mitochondrial Function and Pathology
Jiangxi Science and Technology Normal University
2025
Kaohsiung Armed Forces General Hospital
2024
National Taiwan University
1990-2024
National Yang Ming Chiao Tung University
2016-2020
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...
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...
ABSTRACT Ergosterol is an important component of fungal cell membranes and participates in the regulation its fluidity, permeability, material transport. In our study, we found that ergosterol biosynthesis pathway Aspergillus oryzae more complex than Saccharomyces cerevisiae , involving 49 enzymes 25 reactions. this systematically analyzed expression pattern subcellular localization A. synthases their effects on fatty acid metabolism. The results showed synthase genes were distributed across...
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,...
Targeting thymidylate kinase (TMPK) that catalyzes the phosphotransfer reaction for formation of dTDP from dTMP is a new strategy anticancer treatment. This study to understand inhibitory mechanism previously identified human TMPK (hTMPK) inhibitor YMU1 (1a) by molecular docking, isothermal titration calorimetry, and photoaffinity labeling. The dynamics simulation suggests 1a prefers binding at catalytic site hTMPK, whereas hTMPK inhibitors bear pyridino[d]isothiazolone or...
The yeast Candida albicans is the most prevalent opportunistic fungal pathogen in humans. Drug resistance among C. isolates poses a common challenge, and overcoming this represents an unmet need managing pathogen. Here, we investigated CDC8, encoding thymidylate kinase (TMPK), as potential drug target for management of infections. We found that region spanning amino acids 106-123, namely Ca-loop TMPK (CaTMPK), contributes to hyperactivity enzyme compared with human (hTMPK) utilization...
Abstract The levels of the four deoxynucleoside triphosphates (dNTPs) are under strict control in cell, as improper or imbalanced dNTP pools may lead to growth defects and oncogenesis. Upon treatment cancer cells with therapeutic agents, changes canonical dNTPs provide critical information for evaluating drug response mode action. radioisotope-labeling enzymatic assay has been commonly used quantitation cellular levels. However, disadvantage this method is handling biohazard materials. Here,...
Measurement of four dNTP pools is important for investigating metabolism, genome stability, and drug action. In this report, we developed a two-step method quantitating dNTPs by the combination rolling circle amplification (RCA) quantitative polymerase chain reaction (qPCR). We used CircLigase to generate single-strand DNA in circular monomeric configuration, which was then first step RCA that contained three excess quantification one at limiting levels. The second products qPCR, primer...
Abstract T315I mutation of Bcr-Abl in chronic myeloid leukemia (CML) leads to therapeutic resistance. It is known that transformation causes ROS-induced DNA damages and replication stress, which can be exploited for anti-nucleotide therapy. We developed a small compound, JMF4073, inhibited pyrimidylate kinases selectively eliminated Bcr-Abl-transformed, but not untransformed cells, due dTTP exhaustion stress. However, T315I-Bcr-Abl-transformed cells were less vulnerable JMF4073 because...
Abstract T315I mutation of Bcr-Abl in chronic myeloid leukemia (CML) leads to therapeutic resistance. It is known that transformation causes ROS-induced DNA damage, which can be exploited for anti-nucleotide treatment. We developed a small compound, JMF4073, inhibits pyrimidylate kinases. Intriguingly, treatment JMF4073 selectively eliminated WT-, but not T315I-, Bcr-Abl-transformed cells. found the higher level cellular glutathione(GSH) T315I-Bcr-Abl cells confers replication fork...
Abstract The ability to overcome drug resistance in outbreaks of Candida albicans infection is an unmet need health management. Here, we investigated CDC8 , which encodes thymidylate kinase (TMPK), as a potential target for the treatment C. infection. In this study, found that specific region spanning amino acids 106-123, namely, Ca-loop TMPK (CaTMPK) contributes hyperactivity enzyme compared human (hTMPK) and utilization deoxyuridine monophosphate (dUMP)/ deoxy-5-Fluorouridine (5-FdUMP)...