A5017217837- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Diet, Metabolism, and Disease
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- Adipokines, Inflammation, and Metabolic Diseases
- Endoplasmic Reticulum Stress and Disease
- Exercise and Physiological Responses
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Cancer, Lipids, and Metabolism
- DNA Repair Mechanisms
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
- Inflammatory mediators and NSAID effects
Ulsan National Institute of Science and Technology
2015-2025
Institute for Basic Science
2022-2023
Korea University of Science and Technology
2021
Harvard University
2010-2018
Dana-Farber Cancer Institute
2011-2018
Ulsan College
2016
Pohang University of Science and Technology
2000-2008
Dysregulation of O-GlcNAc modification catalyzed by transferase (OGT) and O-GlcNAcase (OGA) contributes to the etiology chronic diseases aging, including cancer, cardiovascular disease, type 2 diabetes, Alzheimer's disease. Here we found that natural aging in wild-type mice was marked a decrease OGA OGT protein levels an increase O-GlcNAcylation various tissues. Genetic disruption resulted constitutively elevated embryos led neonatal lethality with developmental delay. Importantly, observed...
Peroxisome proliferator-activated receptors (PPARα, -β/δ, and -γ) are a subfamily of nuclear that plays key roles in glucose lipid metabolism. PPARγ is the molecular target thiazolidinedione class antidiabetic drugs has many side effects. also activated by long chain unsaturated or oxidized/nitrated fatty acids, but its relationship with medium acids remains unclear even though triglyceride oils have been used to control weight gain glycemic index. Here, we show decanoic acid (DA), 10-carbon...
Blocking phosphorylation of peroxisome proliferator-activated receptor (PPAR)γ at Ser(273) is one the key mechanisms for antidiabetes drugs to target PPARγ. Using high-throughput screening, we here describe that Gleevec blocks cyclin-dependent kinase 5-mediated PPARγ devoid classical agonism as a antagonist ligand. In high fat-fed mice, improved insulin sensitivity without causing severe side effects associated with other PPARγ-targeting drugs. Furthermore, reduces lipogenic and...
PGC-1α is a transcriptional coactivator that powerfully regulates many pathways linked to energy homeostasis. Specifically, controls mitochondrial biogenesis in most tissues but also initiates important tissue-specific functions, including fiber type switching skeletal muscle and gluconeogenesis fatty acid oxidation the liver. We show here S6 kinase, activated liver upon feeding, can phosphorylate directly on two sites within its arginine/serine-rich (RS) domain. This phosphorylation...
Voluntary exercise is known to have an antidepressant effect. However, the underlying mechanism for this action of remains unclear, and little progress has been made in identifying genes that are directly involved. We identified macrophage migration inhibitory factor (MIF) by analyzing existing mRNA microarray data confirmed augmented expression selected under two experimental conditions: voluntary electroconvulsive seizure. A proinflammatory cytokine, MIF expressed central nervous system...
// Yong Ryoul Yang 1 , Dae Hyun Kim Young-Kyo Seo Dohyun Park 2 Hyun-Jun Jang 1,2 Soo Youn Choi Hwa Lee Gyun Hui Kazuki Nakajima 3 Naoyuki Taniguchi Jung-Min Eun-Jeong Hyo Youl Moon Il Shin Ho 4 Sung Ryu Lucio Cocco 5 and Pann-Ghill Suh School of Life Sciences, Ulsan National Institute Science Technology, Ulsan, Republic Korea Division Molecular Science, Pohang University Pohang, Kyungbuk, Disease Glycomics Team, Systems Glycobiology Research Group, RIKENMax Planck Joint Center, Global...
Phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) at Ser273 by cyclin-dependent kinase 5 (CDK5) in adipose tissue stimulates insulin resistance, but the underlying molecular mechanisms are unclear. We show here that Thrap3 (thyroid hormone receptor-associated protein 3) can directly interact with PPARγ when it is phosphorylated Ser273, and this interaction controls diabetic gene programming mediated phosphorylation PPARγ. Knockdown restores most genes dysregulated CDK5...
Significance Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that plays central role in the formation of adipose tissue. We show phosphorylation single amino acid PPARγ alters response cells to DNA damaging agents, including multiple types chemotherapy. Noncanonical agonist ligands block sensitize variety cancer cell these chemotherapeutic agents vitro and vivo. interacts with tumor-suppressor p53 manner dependent on at S273. These data strongly suggest...
We revealed the X-ray structure of PPARγ co-crystallized with SR1664 bound to alternate binding site and confirmed that this blocks phosphorylation Ser273.
Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in metabolism the liver. Although nuclear receptors (NRs) play a crucial role hepatic metabolism, underlying mechanisms of NR regulation NAFLD remain largely unclear. Methods: Using network analysis RNA-seq to determine correlation between NRs microRNA human patients, we revealed that MIR20B specifically targets PPARA. mimic anti- were administered HepG2 Huh-7 cells mouse...
An ideal cancer therapeutic strategy involves the selective killing of cells without affecting surrounding normal cells. However, researchers have failed to develop such methods for achieving cell death because shared features between cancerous and In this study, we developed a called cancer-specific insertions-deletions (InDels) attacker (CINDELA) selectively induce using CRISPR-Cas system. CINDELA utilizes previously unexplored idea introducing CRISPR-mediated DNA double-strand breaks...
Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one the major pathogenic factors contributing to progression nonalcoholic fatty liver disease (NAFLD). involved breakdown intracellular lipids maintenance healthy mitochondria NAFLD. However, mechanisms underlying dysregulation NAFLD remain unclear. Here, we demonstrate that hepatic expression level Thrap3 was significantly increased conditions. Liver-specific knockout improved lipid...
Replication protein A (RPA), a eukaryotic single-stranded DNA (ssDNA) binding protein, dynamically interacts with ssDNA in different modes and plays essential roles metabolism such as replication, repair, recombination. RPA accumulation on due to replication stress triggers the damage response (DDR) by activating ataxia telangiectasia RAD3-related (ATR) kinase, which phosphorylates itself downstream DDR factors, including RPA. We recently reported that N-methyl-D-aspartate receptor...
Apoptosis is a cell suicide mechanism that requires the activation of cellular death proteases for its induction. We examined whether progress apoptosis involves cleavage phospho-lipase C-γΙ (PLC-γΙ), which plays pivotal role in mitogenic signaling pathway. Pretreatment T leu-kemic Molt-4 cells with PLC inhibitors such as U-73122 or ET-18-OCH3 potentiated etoposide-in-duced these cells. PLC-γΙ was fragmented when were treated several apoptotic stimuli etoposide, ceramides, and tumor necrosis...
3′‐Phosphoinositide‐dependent kinase‐1 (PDK1) has been identified for its ability to phosphorylate and activate Akt. Accumulated studies have shown that the activation of PDK1/Akt pathway plays a pivotal role in cell survival, proliferation, tumorigenesis. Therefore, is believed be critical target cancer intervention. In this paper, we report discovery new function phenothiazines, widely known as antipsychotics, inhibiting pathway. Upon epidermal growth factor (EGF) stimulation,...