Publications by authors named "Yeongmi Cheon"

9 Publications

  • Page 1 of 1

Na/K-ATPase beta1-subunit associates with neuronal growth regulator 1 (NEGR1) to participate in intercellular interactions.

BMB Rep 2021 Mar;54(3):164-169

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea.

Neuronal growth regulator 1 (NEGR1) is a GPI-anchored membrane protein that is involved in neural cell adhesion and communication. Multiple genome wide association studies have found that NEGR1 is a generic risk factor for multiple human diseases, including obesity, autism, and depression. Recently, we reported that Negr1-/- mice showed a highly increased fat mass and affective behavior. In the present study, we identified Na/K-ATPase, beta1-subunit (ATP1B1) as an NEGR1 binding partner by yeast two-hybrid screening. NEGR1 and ATP1B1 were found to form a relatively stable complex in cells, at least partially co-localizing in membrane lipid rafts. We found that NEGR1 binds with ATP1B1 at its C-terminus, away from the binding site for the alpha subunit, and may contribute to intercellular interactions. Collectively, we report ATP1B1 as a novel NEGR1-interacting protein, which may help deciphering molecular networks underlying NEGR1-associated human diseases. [BMB Reports 2021; 54(3): 164-169].
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

MAM domain containing 2 is a potential breast cancer biomarker that exhibits tumour-suppressive activity.

Cell Prolif 2020 Sep 24;53(9):e12883. Epub 2020 Jul 24.

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, Republic of Korea.

Objectives: The aim of this study was to discover new potential biomarkers of breast cancer and investigate their cellular functions.

Materials And Methods: We analysed the gene expression profiles of matched pairs of breast tumour and normal tissues from 24 breast cancer patients. Tetracycline-inducible MAMDC2 expression system was established and used to evaluate cell proliferation in vitro and in vivo. MAMDC2-mediated signalling was determined using immunoblot analysis.

Results: We identified MAMDC2 as a down-regulated gene showing significant prognostic capability. Overexpression of MAMDC2 or treatment with MAMDC2-containing culture medium significantly inhibited the cell proliferation of T-47D cells. Furthermore, MAMDC2 expression reduced in vivo growth of T-47D xenograft tumours. MAMDC2 may exert its growth-inhibitory functions by attenuating the MAPK signalling pathway.

Conclusion: We report that MAMDC2 has a tumour-suppressive role and, as a secretory protein, it might be useful as a biomarker for breast cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.12883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507446PMC
September 2020

Actin-microtubule crosslinker Pod-1 tunes PAR-1 signaling to control synaptic development and tau-mediated synaptic toxicity.

Neurobiol Aging 2020 06 14;90:93-98. Epub 2020 Feb 14.

Gwangju Center, Korea Basic Science Institute (KBSI), Gwangju, South Korea. Electronic address:

Partitioning-defective 1 (PAR-1), a conserved cell polarity regulator, plays an important role in synaptic development, and its mutation affects the formation of synaptic boutons and localization of postsynaptic density protein Discs large (Dlg) at the neuromuscular junction (NMJ) in Drosophila. Drosophila PAR-1 and its human homolog, Microtubule affinity-regulating kinases (MARK), are also known to be implicated in Alzheimer's disease (AD) by controlling tau-mediated Aβ toxicity. However, the molecular mechanisms of PAR-1 function remain incompletely understood. Here we identified Pod-1, an actin-microtubule crosslinker, which functionally and physically interacts with PAR-1 in Drosophila. Pod-1 prominently co-localizes with PAR-1 in the postsynaptic region and regulates PAR-1 activity at the NMJ. Synaptic defects, including the reduction of boutons and delocalization of Dlg caused by PAR-1 overexpression, were rescued by Pod-1 knockdown. Conversely, the reduction of synaptic boutons in PAR-1 overexpressed NMJ was synergistically enhanced by the overexpression of Pod-1. Furthermore, Pod-1 increases the PAR-1 dependent S262 phosphorylation of tau, which is known to contribute to tau-mediated Aβ toxicity. In line with the change of tau phosphorylation, Pod-1 knockdown rescued tau-mediated synaptic toxicity at the NMJ. Our results suggest that Pod-1 may act as a modulator of PAR-1 in synaptic development and tau-mediated toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2020.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358005PMC
June 2020

Label-Free Tomographic Imaging of Lipid Droplets in Foam Cells for Machine-Learning-Assisted Therapeutic Evaluation of Targeted Nanodrugs.

ACS Nano 2020 02 10;14(2):1856-1865. Epub 2020 Jan 10.

Department of Systems Biotechnology , Chung-Ang University , Anseong , Gyeonggi 17546 , Korea.

Lipid droplet (LD) accumulation, a key feature of foam cells, constitutes an attractive target for therapeutic intervention in atherosclerosis. However, despite advances in cellular imaging techniques, current noninvasive and quantitative methods have limited application in living foam cells. Here, using optical diffraction tomography (ODT), we performed quantitative morphological and biophysical analysis of living foam cells in a label-free manner. We identified LDs in foam cells by verifying the specific refractive index using correlative imaging comprising ODT integrated with three-dimensional fluorescence imaging. Through time-lapse monitoring of three-dimensional dynamics of label-free living foam cells, we precisely and quantitatively evaluated the therapeutic effects of a nanodrug (mannose-polyethylene glycol-glycol chitosan-fluorescein isothiocyanate-lobeglitazone; MMR-Lobe) designed to affect the targeted delivery of lobeglitazone to foam cells based on high mannose receptor specificity. Furthermore, by exploiting machine-learning-based image analysis, we further demonstrated therapeutic evaluation at the single-cell level. These findings suggest that refractive index measurement is a promising tool to explore new drugs against LD-related metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b07993DOI Listing
February 2020

Two major alternative splice variants of beta-TrCP1 interact with CENP-W with different binding preferences.

Genes Genomics 2019 02 28;41(2):167-174. Epub 2018 Sep 28.

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, South Korea.

Beta-transducin repeat containing protein 1 (β-TrCP1) is a versatile F-box protein that is responsible for substrate recognition of SCF ubiquitin ligase. In human cells, two major alternatively spliced isoforms (b and f) of β-TrCP1 were found. Recently, we identified that CENP-W interacts with the β-TrCP1 and regulates the cellular distribution of β-TrCP1. In this study, we examined whether CENP-W, a new kinetochore component, may differentially regulate the two major isoforms of human β-TrCP1 (b and f), especially in the cytoplasmic-nuclear shuttling of β-TrCP1. An in vivo binding assay was performed to examine whether CENP-W binds differently to the two isoforms of β-TrCP1. EGFP-conjugated β-TrCP1 isoforms were co-transfected with NLS-defective mutant CENP-W and their cellular distribution were observed using a fluorescence microscopy. Although CENP-W interacts with both b and f isoforms, it has a greater affinity for the b isoform rather than f isoform. Moreover, CENP-W effectively regulates the nuclear-cytoplasmic shuttling of these two β-TrCP1 isoforms, but with a slight preference towards the b isoform. The Elongin C-binding motif existing in the b isoform may be involved in their specific association. CENP-W showed a higher affinity toward the β-TrCP1 b isoform, and translocated isoform b more efficiently than isoform f, which may allow a fine regulation of of β-TrCP1 in the cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13258-018-0748-3DOI Listing
February 2019

CENP-W inhibits CDC25A degradation by destabilizing the SCF complex at G/M.

FASEB J 2018 Jun 4:fj201701358RRR. Epub 2018 Jun 4.

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, South Korea.

Skp, Cullin, F-box (SCF) ubiquitin ligases play a central role in cell cycle regulation and tumorigenesis via proteolytic cleavage of many essential cell cycle regulators. In this study, we propose that centromere protein (CENP)-W, a newly identified kinetochore component, is a novel negative regulator of the SCF complex. CENP-W interacts with Cullin (CUL)-1 and β-Transducin repeat-containing protein (β-TrCP)-1 through highly overlapped binding sites with S-phase kinase-associated protein (SKP)-1. CENP-W is incorporated into the SCF complex to promote complex disassembly. Unlike other known regulators that increase SCF ubiquitin ligase activity by promoting complex reassociation, CENP-W-mediated complex disorganization induced β-TrCP1 degradation and consequently decreased its activity. The association between CENP-W and the SCF complex was prominent during the G/M transition in the nucleus. Especially, CENP-W knockdown decreased the cell division cycle-25A protein level, leading to a delay in mitotic progression. We propose that CENP-W participates in cell cycle regulation by modulating SCF ubiquitin ligase activity.-Cheon, Y., Lee, S. CENP-W inhibits CDC25A degradation by destabilizing the SCF complex at G/M.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.201701358RRRDOI Listing
June 2018

Centromere protein W interacts with beta-transducin repeat-containing protein 1 and modulates its subcellular localization.

FEBS Lett 2016 Dec 23;590(24):4441-4452. Epub 2016 Nov 23.

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, Korea.

Beta-transducin repeat-containing protein 1 (β-TrCP1) is a substrate-recognition module of SCF ubiquitin ligases and its subcellular distribution is known to be critical for target specificity. Heterogeneous nuclear ribonucleoprotein (hnRNP) U, an abundant nuclear protein, is known to be a unique regulator of β-TrCP1 shuttling between the cytoplasm and the nucleus. In this study, we report that centromere protein W (CENP-W), which is frequently overexpressed in a variety of human cancers, may also contribute to β-TrCP1 shuttling. Although hnRNP U and CENP-W can interact with β-TrCP1 and transport it independently, these proteins do not compete for β-TrCP1 binding, but rather cooperate to form a stable shuttling complex. Intriguingly, we found that overexpression of CENP-W leads to accumulation of β-TrCP1 in the nucleus. Thus, we propose that CENP-W may function as a booster of β-TrCP1 nuclear import to increase the oncogenicity of β-TrCP1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1873-3468.12483DOI Listing
December 2016

New centromeric component CENP-W is an RNA-associated nuclear matrix protein that interacts with nucleophosmin/B23 protein.

J Biol Chem 2011 Dec 14;286(49):42758-42769. Epub 2011 Oct 14.

Department of Microbiology and Molecular Biology, Chungnam National University, 305-764, Daejeon, Republic of Korea. Electronic address:

CENP-W was originally identified as a putative oncogene, cancer-upregulated gene 2 (CUG2) that was commonly up-regulated in many cancer tissues. Recently, CENP-W has also been identified as a new centromeric component that interacts with CENP-T. As a complex with CENP-T, CENP-W plays crucial roles in assembly of the functional kinetochore complex. In this study, the subnuclear localization of CENP-W was extensively analyzed using various approaches. We found that ectopically expressed CENP-W primarily accumulated in the nucleolus and remained substantially associated with the nucleolus in stable cells. The following fractionation study also showed that CENP-W is associated with RNA as well as DNA. Moreover, a considerable amount of CENP-W was found in the nuclear mesh-like structure, nuclear matrix, possibly indicating that CENP-W participates in diverse subnuclear activities. Finally, biochemical affinity binding analysis revealed that CENP-W specifically interacts with the nucleolar phosphoprotein, nucleophosmin (B23). Depletion of cellular B23 by siRNA treatment induced a dramatic decrease of CENP-W stability and severe mislocalization during prophase. Our data proposed that B23 may function in the assembly of the kinetochore complex by interacting with CENP-W during interphase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M111.228411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234906PMC
December 2011

Newly identified tumor-associated role of human Sharpin.

Mol Cell Biochem 2010 Jul 24;340(1-2):161-7. Epub 2010 Feb 24.

Department of Microbiology, Chungnam National University, Daejeon 305-764, Korea.

In order to discover previously unidentified cancer-associated genes, we analyzed genome-wide differences in gene expression between tumor biopsies and normal tissues. Among those differentially regulated genes, we identified Sharpin (Shank-associated RH domain-interacting protein) as a commonly up-regulated gene in multiple human cancer types. Although rat Sharpin is reported to interact with Shank1, a multidomain scaffold protein localized in postsynaptic densities, its exact roles are unknown. Whereas human Sharpin homologue was primarily localized in the cytosol of cultured cells, they were detected in both cytosol and nucleus of the cells from ovarian and liver cancer tissues using immunohistochemical staining. In addition, Chinese ovary hamster cells over-expressing Sharpin exhibited enhanced cancer-specific phenotypes in multiple in vitro tumor assays. Taken together, the results suggest that Sharpin is not an inert scaffold protein, but may play tumor-associated roles during cancer biogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-010-0413-xDOI Listing
July 2010