A5061509294- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- Polyamine Metabolism and Applications
- Chemical Synthesis and Analysis
- Immune Response and Inflammation
- Hair Growth and Disorders
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Luminescence and Fluorescent Materials
- interferon and immune responses
- Cellular transport and secretion
- Supramolecular Chemistry and Complexes
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- Erythropoietin and Anemia Treatment
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Skin and Cellular Biology Research
Yonsei University
2021-2024
Gangnam Severance Hospital
2021-2022
Seoul National University
2010-2020
University of Pennsylvania
2014-2016
Seoul National University Hospital
2012
New Generation University College
2010
Silla University
2001
Dongguk University WISE
2001
Dongguk University
2001
A tRNA synthase in metabolic control Leucyl-tRNA synthetase 1 (LARS1), which covalently couples leucine to its cognate transfer RNAs (tRNAs), appears have broader roles the of metabolism. The enzyme also serves as a sensor for mechanistic target rapamycin complex (mTORC1), regulates protein synthesis, metabolism, autophagy, and cell growth. Yoon et al. show that cells deprived glucose, LARS1 is phosphorylated by Unc-51 like autophagy activating kinase (see Perspective Lehman Abraham). This...
Leucyl-tRNA synthetase (LRS) is known to function as leucine sensor in the mammalian target of rapamycin complex 1 (mTORC1) pathway. However, pathophysiological significance its activity not well understood. Here, we demonstrate that for mTORC1 activation LRS can be decoupled from catalytic activity. We identified compounds inhibit leucine-dependent pathway by specifically inhibiting GTPase activating LRS, while affecting For further analysis, selected one compound, BC-LI-0186, which binds...
Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but mechanism of their secretion is not understood. This study describes route ARS lysyl-tRNA synthetase (KRS) how this process regulated by caspase activity, which has been implicated unconventional other proteins. We show KRS from colorectal carcinoma cells within lumen exosomes trigger an inflammatory response. Caspase-8 cleaved...
Despite the explosion in numbers of cancer genomic studies, metastasis is still major cause mortality. In breast cancer, approximately one-fifth metastatic patients survive 5 years. Therefore, detecting at a high risk developing distant first diagnosis critical for effective treatment strategy. We hereby present novel systems biology approach to identify driver mutations escalating based on both exome and RNA sequencing our collected 78 normal-paired cancers. Unlike occurring commonly...
Significance LRS, an enzyme involved in protein synthesis, and Sestrin2, a stress-induced metabolic protein, are suggested to function as leucine sensors for the mTORC1 pathway, central regulator of cell metabolism, growth, proliferation, survival. The Rag GTPase cycle regulates mTORC1; however, regulators their coordination remain unknown. We show dynamics RagD–RagB during signaling describe contrasting yet complementary roles LRS Sestrin2 GTPase–mTORC1 functioning “ON” “OFF” switches,...
Abstract A fundamental question in biology is how vertebrates evolved and differ from invertebrates, little known about differences the regulation of translation two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated initiation machinery that specifically interacts with eIF4E homologous protein, forms structurally analogous to eIF4F-mediated via recruitment other components. Biochemical RNA immunoprecipitation analyses coupled sequencing suggest this emerged as...
A new fluorescent chemosensor, anthryl tetra acid, was synthesized and showed large fluorescence quenching effects in 100% aqueous solution with metal ions via photoinduced electron transfer (PET). Chelatoselective perturbation observed Cd(II) resulted from electrophilic aromatic cadmiation.
Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin been known to be affected by dietary threonine supply since de novo synthesis proteins sensitive luminal concentration. However, it unknown whether...
Leucyl-tRNA synthetase 1 (LARS1) mediates activation of leucine-dependent mechanistic target rapamycin complex (mTORC1) as well ligation leucine to its cognate tRNAs, yet mechanism sensing is poorly understood. Here we describe binding-induced conformational changes LARS1. We determine different crystal structures LARS1 complexed with leucine, ATP, and a reaction intermediate analog, leucyl-sulfamoyl-adenylate (Leu-AMS), find two distinct functional states for mTORC1 activation. Upon binding...
Abstract Prolyl‐tRNA synthetase 1 (PARS1) has attracted much interest in controlling pathologic accumulation of collagen containing high amounts proline fibrotic diseases. However, there are concerns about its catalytic inhibition for potential adverse effects on global protein synthesis. We developed a novel compound, DWN12088, whose safety was validated by clinical phase studies, and therapeutic efficacy shown idiopathic pulmonary fibrosis model. Structural kinetic analyses revealed that...
Abstract All living organisms have the ability to sense nutrient levels coordinate cellular metabolism. Despite importance of nutrient-sensing pathways that detect amino acids and glucose, how availability these two types nutrients is integrated unclear. Here, we show glucose regulates central effector mTORC1 through intracellular leucine sensor leucyl-tRNA synthetase 1 (LARS1). Glucose starvation results in O -GlcNAcylation LARS1 on residue S1042. This modification inhibits interaction with...
The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands Toll-like receptors (TLRs) have been suggested to activate adaptive immune by modulating the function antigen-presenting cells (APCs). Despite their therapeutic potential, development TLR immunotherapy often hampered due rapid systemic toxicity. Regarding safety concerns currently available ligands, finding a new agonist with potent efficacy and...
Abstract Regulation of the heat shock response (HSR) is essential in all living systems. In E. coli , HSR regulated by an alternative σ factor, 32 which encoded rpoH gene. The mRNA adopts a complex secondary structure that critical for proper translation protein. At low temperatures, gene transcript forms highly structured containing several three‐way junctions, including rare perfectly paired junction (3WJ). This serves as primitive but effective strategy thermal control expression. this...
Triptycenes have been shown to bind nucleic acid three-way junctions, but rapid and efficient methods diversify the triptycene core are lacking. An synthesis of a 9-substituted scaffold is reported that can be used as building block for solid-phase peptide diversification. The was diversified produce new class tripeptide-triptycenes, their binding abilities toward d(CAG)·(CTG) repeat junctions were investigated.
Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is known to associated with fibrosis through its catalytic activity produce prolyl-tRNA. Although inhibitor halofuginone (HF) has been inhibit the TGF-β pathway as well reduce prolyl-tRNA production for control of fibrosis, underlying mechanism how EPRS1 regulates was not fully understood. Here, we show a noncatalytic function in controlling and hepatic stellate cell activation via interaction receptor I (TβRI). Upon stimulation TGF-β, phosphorylated...
Recently, the utility of triptycene as a scaffold for targeting nucleic acid three-way junctions was demonstrated. A rapid, efficient route synthesis bridgehead-substituted triptycenes is reported, in addition to solid-phase diversification new class peptides. The peptides were evaluated binding d(CAG)·(CTG) repeat DNA junction exhibiting potent affinities. provide building blocks rapid access diverse ligands with novel architectures.
Adipogenesis is known to be controlled by the concerted actions of transcription factors and co-regulators. However, little about regulation mechanism that control adipogenesis. In addition, adipogenic roles translational remain unclear. Here, we show aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), an auxiliary factor associated with a macromolecular tRNA synthetase complex, negatively regulates adipogenesis via direct interaction DNA-binding domain peroxisome...
Hair follicle stem cells (HFSCs) and dermal papilla (DPCs) are crucial in the biogenesis maintenance of hair follicles (HFs). This study demonstrated that a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) secreted HFSCs activated DPCs maintained HF homeostasis. A histological analysis revealed AIMP1 levels decreased with loss. regrowth AIMP1-induced mice was faster than non-induced mice. Deletion mapping 41 amino acids (TN41, aa 6-46) as active...