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Dive into the research topics where Nuri Yun is active.

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Featured researches published by Nuri Yun.


Neurochemistry International | 2010

Proteomic analysis of expression and protein interactions in a 6-hydroxydopamine-induced rat brain lesion model.

Bokyung Park; Junyoung Yang; Nuri Yun; Kwang Min Choe; Byung Kwan Jin; Young Jun Oh

Parkinsons disease (PD) is the second most common neurodegenerative disorder caused by selective degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Although mitochondrial abnormality, oxidative stress and proteasomal dysfunction are recognized as major contributors to the progression of PD, there is a limited understanding of the key molecular events that provoke degeneration of DA neurons. Using a proteomic approach, we attempted to identify profiles of proteins with altered expression levels in rats following unilateral stereotaxic injection of 6-hydroxydopamine into the SNc. Protein expression profiles of these proteins in the substantia nigra and the striatum were made using two-dimensional gel electrophoresis in conjunction with a mass spectrometry. More than 70 identified proteins displayed significant differences in their temporal and spatial expression pattern between experimental and vehicle-operated control groups. Based on the identity of the proteins, we further searched for potential binding partners using biological databases available on the web and constructed a protein interaction network. Among several interconnected proteins in the network, we verified the interaction between prohibitin and the NADH-ubiquinone oxidoreductase 30kDa subunit (NDUFS3 subunit; a mitochondrial complex I subunit) by co-immunoprecipitation. We also confirmed, using immunohistochemical localization, that both prohibitin and the NDUFS3 subunit were increased in the dying DA neurons, suggesting its potential role in regulating mitochondrial function in dying DA neurons. Furthermore, knockdown of prohibitin accelerated 6-hydroxydopamine-induced cell death in SH-SY5Y cells. Our results raise the possibility that interconnected proteins in the network may positively or negatively impact the progression of DA neuronal death.


Cell Death & Differentiation | 2016

Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death

Chiho Kim; Nuri Yun; Juhyung Lee; Moussa B. H. Youdim; Chung Ju; Won Ki Kim; Pyung Lim Han; Young Jun Oh

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase and its dysregulation is implicated in neurodegenerative diseases. Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5-mediated phosphorylation disrupts the interaction between CHIP and truncated apoptosis-inducing factor (tAIF) without affecting CHIP’s E3 ligase activity, resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral transduction assay shows that knockdown of Cdk5 or overexpression of CHIPS20A, but not CHIPWT, attenuates tAIF-mediated neuronal cell death induced by hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP negatively regulates its neuroprotective function, thereby contributing to neuronal cell death progression following neurotoxic stimuli.


Journal of Biological Chemistry | 2013

Gel-based Protease Proteomics for Identifying the Novel Calpain Substrates in Dopaminergic Neuronal Cell

Chiho Kim; Nuri Yun; Young Mook Lee; Jae Y. Jeong; Jeong Y. Baek; Hwa Young Song; Chung Ju; Moussa B.H. Youdim; Byung Kwan Jin; Won Ki Kim; Young Jun Oh

Background: It is important to assess contribution of calpain activation and identify substrates affected during neurodegeneration. Results: Gel-based protease proteomics identified novel substrates that were cleaved in neurotoxin-treated culture and rat brain disease models. Conclusion: These novel calpain substrates may confer protection against neurodegeneration. Significance: Our findings contribute to better deciphering the molecular mechanism underlying the progression of protease-mediated neurodegeneration. Calpains are a family of calcium-dependent cysteine proteases that are ubiquitously expressed in mammals and play critical roles in neuronal death by catalyzing substrate proteolysis. Here, we developed two-dimensional gel electrophoresis-based protease proteomics to identify putative calpain substrates. To accomplish this, cellular lysates from neuronal cells were first separated by pI, and the immobilized sample on a gel strip was incubated with a recombinant calpain and separated by molecular weight. Among 25 altered protein spots that were differentially expressed by at least 2-fold, we confirmed that arsenical pump-driving ATPase, optineurin, and peripherin were cleaved by calpain using in vitro and in vivo cleavage assays. Furthermore, we found that all of these substrates were cleaved in MN9D cells treated with either ionomycin or 1-methyl-4-phenylpyridinium, both of which cause a calcium-mediated calpain activation. Their cleavage was blocked by calcium chelator or calpain inhibitors. In addition, calpain-mediated cleavage of these substrates and its inhibition by calpeptin were confirmed in a middle cerebral artery occlusion model of cerebral ischemia, as well as a stereotaxic brain injection model of Parkinson disease. Transient overexpression of each protein was shown to attenuate 1-methyl-4-phenylpyridinium-induced cell death, indicating that these substrates may confer protection of varying magnitudes against dopaminergic injury. Taken together, the data indicate that our protease proteomic method has the potential to be applicable for identifying proteolytic substrates affected by diverse proteases. Moreover, the results described here will help us decipher the molecular mechanisms underlying the progression of neurodegenerative disorders where protease activation is critically involved.


Journal of Neural Transmission | 2011

Nuclear translocation of anamorsin during drug-induced dopaminergic neurodegeneration in culture and in rat brain.

Kyung Ah Park; Nuri Yun; Dong Ik Shin; So Yoen Choi; Hyun Kim; Won Ki Kim; Yuzuru Kanakura; Hirohiko Shibayama; Young Jun Oh

Anamorsin, also called cytokine-induced apoptosis inhibitor 1 (CIAPIN1), was recently identified to confer resistance to apoptosis induced by growth factor deprivation and to be indispensible for hematopoiesis. Recently, it was demonstrated that anamorsin is also widely distributed in both fetal and adult tissues. In this study, we evaluated the tissue distribution of anamorsin in the central nervous system (CNS) during development. In situ hybridization and immunoblot analyses revealed that anamorsin mRNA and protein were both highly and widely expressed in various regions of the CNS, including the cerebral cortex, hippocampus, midbrain, cerebellum, medulla, and spinal cord. Based on these findings, we examined its cellular localization during drug-induced neurodegeneration in MN9D dopaminergic cells. Both immunocytochemical localization and immunoblot analyses indicated that cytosolic anamorsin was translocated into the nucleus in a time-dependent manner following treatment with a reactive oxygen species (ROS)-inducing drug, 6-hydroxydopamine (6-OHDA). Treatment of cells with the apoptosis-inducing reagent, staurosporine, did not appear to cause translocation of anamorsin into the nucleus. When cells were treated with the nuclear export inhibitor, Leptomycin B, alone or with 6-OHDA, nuclear anamorsin levels increased, indicating that nuclear influx and efflux of anamorsin are regulated by 6-OHDA treatment. In rat brain injected with 6-OHDA, nuclear translocation of anamorsin was identified in certain tyrosine hydroxylase (TH)-positive neurons as well as TH-negative cells. Furthermore, treatment of MN9D cells with hydrogen peroxide or ROS-inducing trace metals caused nuclear translocation of anamorsin. Taken together, our data indicate that nuclear translocation of anamorsin is a ROS-dependent event and may participate in the regulation of transcription of critical molecules during dopaminergic neurodegeneration.


Biochemical and Biophysical Research Communications | 2014

Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

Juhyung Lee; Nuri Yun; Chiho Kim; Min Young Song; Kang Sik Park; Young Jun Oh

Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.


Biochemical and Biophysical Research Communications | 2013

Caspase-3-mediated cleavage of PICOT in apoptosis

Nuri Yun; Chiho Kim; Hyeseon Cha; Woo Jin Park; Hirohiko Shibayama; Il Seon Park; Young Jun Oh

Mammalian protein kinase C-interacting cousin of thioredoxin (PICOT) is a multi-domain mono-thiol glutaredoxin that is involved in several signal transduction pathways and is necessary for cell growth and metastasis. Here, we demonstrate that PICOT is a cleavage substrate of the apoptosis-related protein caspase-3. In vitro cleavage assays indicated that PICOT was specifically cleaved by caspase-3. Similarly, endogenous PICOT was cleaved in cell death responses induced by staurosporine and etoposide. These phenomena were blocked in the presence of a pan-caspase inhibitor. Using site-directed mutagenesis, we identified two putative caspase-3 cleavage sequences in PICOT, DRLD(101)/G and EELD(226)/T. Interestingly, overexpression of either PICOT wild type or the D101A/D226A double point mutant accelerated etoposide-induced activation of caspase-3 whereas siRNA-mediated knockdown of PICOT blocked this phenomenon. Our data raise the possibility that the pro-apoptotic role of PICOT is actively regulated via caspase-3-mediated cleavage.


Journal of Biological Chemistry | 2014

Anamorsin, a Novel Caspase-3 Substrate in Neurodegeneration

Nuri Yun; Young Mook Lee; Chiho Kim; Hirohiko Shibayama; Akira Tanimura; Yuri Hamanaka; Yuzuru Kanakura; Il Seon Park; Areum Jo; Joo Ho Shin; Chung Ju; Won Ki Kim; Young Jun Oh

Background: It is crucial to identify caspase-3 substrates and their roles during neurodegeneration. Results: Our approach identified 46 novel substrates. Furthermore, we found that anamorsin was cleaved by caspase-3 and mapped its cleavage site. Conclusion: Anamorsin may play an antiapoptotic role in the central nervous system. Significance: Our findings contribute to understanding the molecular mechanism underlying role for anamorsin in caspase-3-mediated cell death. Activated caspases play a central role in the execution of apoptosis by cleaving endogenous substrates. Here, we developed a high throughput screening method to identify novel substrates for caspase-3 in a neuronal cell line. Critical steps in our strategy consist of two-dimensional electrophoresis-based protein separation and in vitro caspase-3 incubation of immobilized proteins to sort out direct substrates. Among 46 putative substrates identified in MN9D neuronal cells, we further evaluated whether caspase-3-mediated cleavage of anamorsin, a recently recognized cell death-defying factor in hematopoiesis, is a general feature of apoptosis. In vitro and cell-based cleavage assays indicated that anamorsin was specifically cleaved by caspase-3 but not by other caspases, generating 25- and 10-kDa fragments. Thus, in apoptosis of neuronal and non-neuronal cells induced by various stimuli including staurosporine, etoposide, or 6-hydroxydopamine, the cleavage of anamorsin was found to be blocked in the presence of caspase inhibitor. Among four tetrapeptide consensus DXXD motifs existing in anamorsin, we mapped a specific cleavage site for caspase-3 at DSVD209↓L. Intriguingly, the 25-kDa cleaved fragment of anamorsin was also detected in post-mortem brains of Alzheimer and Parkinson disease patients. Although the RNA interference-mediated knockdown of anamorsin rendered neuronal cells more vulnerable to staurosporine treatment, reintroduction of full-length anamorsin into an anamorsin knock-out stromal cell line made cells resistant to staurosporine-induced caspase activation, indicating the antiapoptotic function of anamorsin. Taken together, our approach seems to be effective to identify novel substrates for caspases and has the potential to provide meaningful insights into newly identified substrates involved in neurodegenerative processes.


Scientific Reports | 2018

The acetylation of cyclin-dependent kinase 5 at lysine 33 regulates kinase activity and neurite length in hippocampal neurons

Juhyung Lee; Yeon Uk Ko; Yuhyun Chung; Nuri Yun; Myung-Jin Kim; Kyungjin Kim; Young Jun Oh

Cyclin-dependent kinase 5 (CDK5) plays a pivotal role in neural development and neurodegeneration. CDK5 activity can be regulated by posttranslational modifications, including phosphorylation and S-nitrosylation. In this study, we demonstrate a novel mechanism by which the acetylation of CDK5 at K33 (Ac-CDK5) results in the loss of ATP binding and impaired kinase activity. We identify GCN5 and SIRT1 as critical factor controlling Ac-CDK5 levels. Ac-CDK5 achieved its lowest levels in rat fetal brains but was dramatically increased during postnatal periods. Intriguingly, nuclear Ac-CDK5 levels negatively correlated with neurite length in embryonic hippocampal neurons. Either treatment with the SIRT1 activator SRT1720 or overexpression of SIRT1 leads to increases in neurite length, whereas SIRT1 inhibitor EX527 or ectopic expression of acetyl-mimetic (K33Q) CDK5 induced the opposite effect. Furthermore, the expression of nuclear-targeted CDK5 K33Q abolished the SRT1720-induced neurite outgrowth, showing that SIRT1 positively regulates neurite outgrowth via deacetylation of nuclear CDK5. The CDK5 activity-dependent increase of neurite length was mediated by enhanced transcriptional regulation of BDNF via unknown mechanism(s). Our findings identify a novel mechanism by which acetylation-mediated regulation of nuclear CDK5 activity plays a critical role in determining neurite length in embryonic neurons.


Biochemical and Biophysical Research Communications | 2018

Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes

Hyoeun Kim; Nuri Yun; Dasom Mun; Ji Young Kang; Seung-Hyun Lee; Hyelim Park; Hyewon Park; Boyoung Joung


International Journal of Arrhythmia | 2017

Ondansetron Inhibits Voltage-Gated K + Current of Ventricular Myocytes from Pregnant Mouse

Shanyu Cui; Hyewon Park; Hyelim Park; Dasom Mun; Hyoeun Kim; Nuri Yun; Boyoung Joung

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Young Mook Lee

University of Colorado Denver

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Areum Jo

Sungkyunkwan University

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