A5069665291- Cancer-related Molecular Pathways
- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Rare Diseases
- Cancer Research and Treatments
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- TGF-β signaling in diseases
- Neurofibromatosis and Schwannoma Cases
- Melanoma and MAPK Pathways
- DNA Repair Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Gastric Cancer Management and Outcomes
- Redox biology and oxidative stress
- RNA Interference and Gene Delivery
- Glutathione Transferases and Polymorphisms
- Mechanisms of cancer metastasis
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Microtubule and mitosis dynamics
- Cytokine Signaling Pathways and Interactions
Pusan National University
2015-2024
PRG S&Tech (South Korea)
2023
Brandeis University
2022
National Cancer Center
2012-2019
Kyung Hee University
1999-2017
Chung-Ang University
2005-2017
Hanyang University
2013-2016
Institute of Natural Science
2012-2013
Busan Medical Center
2012-2013
Catholic University of Korea
2013
Autosomal-recessive juvenile parkinsonism (AR-JP) is caused by loss-of-function mutations of the parkin gene. Parkin, a RING-type E3 ubiquitin ligase, responsible for ubiquitination and degradation substrate proteins that are important in survival dopamine neurons Parkinson's disease (PD). Accordingly, abnormal accumulation neurotoxic substrates attributable to loss function may be cause neurodegeneration parkin-related parkinsonism. We evaluated known identified date null mice determine...
The melanization reaction induced by activated phenoloxidase in arthropods must be tightly controlled because of excessive formation quinones and systemic damage to the hosts. However, molecular mechanism which phenoloxidase-induced melanin synthesis is regulated vivo largely unknown. It known that Spätzle-processing enzyme a key production cleaved Spätzle from pro-Spätzle Drosophila Toll pathway. Here, we provide biochemical evidence Tenebrio molitor converts both 79-kDa prophenoloxidase...
Wnt/beta-catenin signaling plays a central role in development and is also involved diverse array of diseases. Binding Wnts to the coreceptors Frizzled LRP6/5 leads phosphorylation PPPSPxS motifs intracellular region inhibition GSK3beta bound scaffold protein Axin. However, it remains unknown how specifically inhibited upon Wnt stimulation. Here, we show that overexpression LRP6 containing Ser/Thr rich cluster motif impairs activity cells. Synthetic peptides strongly inhibit vitro only when...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that caused by silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G generates more accessible splicing donor site than does WT produces an alternatively spliced product called progerin, which also expressed in normal aged cells. In this study, we determined progerin binds directly to lamin A/C induces profound nuclear aberrations. Given observation, performed random screening...
Abstract Nuclear structure and function are governed by lamins, which intermediate filaments that mostly consist of α-helices. Different lamin assembly models have been proposed based on low resolution fragmented structures. However, their mechanisms still poorly understood at the molecular level. Here, we present crystal a long human fragment 3.2 Å allows visualization features full-length protein. The shows an anti-parallel arrangement two coiled-coil dimers, is important for process. We...
Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis, they also function as regulators and signaling molecules in diverse biological processes. Here, we screened 11 different human ARSs to identify the enzyme that is secreted a molecule. Among them, found lysyl-tRNA synthetase (KRS) was from intact cells, its secretion induced by TNF-α. The KRS bound macrophages peripheral blood mononuclear cells enhance TNF-α production their migration. mitogen-activated kinases,...
AIMP2/p38 is a scaffolding protein required for the assembly of macromolecular tRNA synthetase complex. Here, we describe previously unknown function AIMP2 as positive regulator p53 in response to genotoxic stresses. Depletion increased resistance DNA damage-induced apoptosis, and introduction into AIMP2-deficient cells restored susceptibility apoptosis. Upon damage, was phosphorylated, dissociated from multi-tRNA complex, translocated nuclei cells. directly interacts with p53, thereby...
Differentially from other kinds of Ras, oncogenic K-Ras, which is mutated approximately 30% human cancer, does not induce apoptosis and senescence. Here, we provide the evidence that K-Ras abrogates p53 function expression through induction Ataxia telangiectasia-mutated Rad3-related mediated Snail stabilization. directly binds to DNA binding domain diminishes tumor-suppressive p53. Thus, elimination si-RNA can in K-Ras-mutated cells, whereas mutant suppress regardless status. Chemicals,...
Although ARS-interacting multifunctional protein 2 (AIMP2, also named as MSC p38) was first found a component for macromolecular tRNA synthetase complex, it recently discovered to dissociate from the complex and work potent tumor suppressor. Upon DNA damage, AIMP2 promotes apoptosis through protective interaction with p53. However, not demonstrated whether indeed pathologically linked human cancer. In this work, we that splicing variant of lacking exon (AIMP2-DX2) is highly expressed by...
Abstract Cancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated factor (PAF) as a key molecule that controls stemness. PAF is highly expressed in breast but not mammary epithelial (MECs). In MECs, ectopic expression induces anchorage-independent growth CSC marker expression. mouse models, conditional ductal hyperplasia. Moreover, endows MECs...
Leucine-rich repeat kinase 2 (LRRK2) is a gene in which mutation causes Parkinson's disease (PD), and p53 prototype tumor suppressor. In addition, activation of patient with PD has been reported by several studies. Because phosphorylation critical for regulating its activity LRRK2 kinase, we tested whether phosphorylated LRRK2. phosphorylates threonine (Thr) at TXR sites an vitro assay, the T304 T377 were identified as putative residues. An increase phospho-Thr motif was confirmed cells...
Abstract Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span an vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated pharmacokinetic (PK) analysis. Thus, we improved property through chemical modification obtained optimized drug candidate, Progerinin (SLC-D011). This extend...
Abstract p53-mediated cellular senescence has been intensively investigated, because it is important for tumor suppressive function. In addition, p16/INK4A well known to be critical senescence. However, detailed molecular mechanism or relevance between p53 and p16-mediated not demonstrated yet. Here we show that induces p16 through Lamin A/C stabilization via direct interaction. Stabilized promotes degradation of BMI-1 MEL-18 (Polycomb repressor complex 1, PRC1), which sequesters promotor....