Ki-Young Lee

Sungkyunkwan University, Sŏul, Seoul, South Korea

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Publications (54)239.43 Total impact

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    ABSTRACT: HP0268 is a conserved, uncharacterized protein from Helicobacter pylori. Here, we determined the solution structure of HP0268 using three-dimensional nuclear magnetic resonance (NMR) spectroscopy, revealing that this protein is structurally most similar to a small MutS-related (SMR) domain that exhibits nicking endonuclease activity. We also demonstrated for the first time that HP0268 is a nicking endonuclease and a purine-specific ribonuclease through gel electrophoresis and fluorescence spectroscopy. The nuclease activities for DNA and RNA were maximally increased by Mn(2+) and Mg(2+) ions, respectively, and decreased by Cu(2+) ions. Using NMR chemical shift perturbations, the metal and nucleotide binding sites of HP0268 were determined to be spatially divided but close to each other. The lysine residues (Lys7, Lys11 and Lys43) are clustered and form the nucleotide binding site. Moreover, site-directed mutagenesis was used to define the catalytic active site of HP0268, revealing that this site contains two acidic residues, Asp50 and Glu54, in the metal binding site. The nucleotide binding and active sites are not conserved in the structural homologues of HP0268. This study will contribute to improving our understanding of the structure and functionality of a wide spectrum of nucleases. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 04/2015; DOI:10.1093/nar/gkv348 · 8.81 Impact Factor
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    ABSTRACT: The ywpF gene (SAV2097) of the Staphylococcus aureus strain Mu50 encodes the YwpF protein, which may play a role in antibiotic resistance. Here, we report the first crystal structure of the YwpF superfamily from S. aureus at 2.5 Å resolution. The YwpF structure consists of two regions: an N-terminal core β-barrel domain that shows structural similarity to type VI secretion system (T6SS) proteins (e.g. Hcp1, Hcp3, and EvpC) and a C-terminal two-helix pair. Although the monomer structure of S. aureus YwpF resembles those of T6SS proteins, the dimer/tetramer model of S. aureus YwpF is distinct from the functionally important hexameric ring of T6SS proteins. We therefore suggest that the S. aureus YwpF may have a different function compared to T6SS proteins. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Proteins Structure Function and Bioinformatics 02/2015; 83(4). DOI:10.1002/prot.24774 · 2.92 Impact Factor
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    ABSTRACT: ECSIT (evolutionarily conserved signaling intermediate in Toll pathways) is known as a multifunctional regulator in different signals, including TLRs, TGF-beta, and BMP. Here, we report a new regulatory role of ECSIT in TLR4-mediated signal. By LPS stimulation, ECSIT endogenously formed a high mass signaling complex including TRAF6 and TAK1, in which ECSIT interacted with each protein and regulated TAK1 activity, leading to the activation of NF-κB. ECSIT-knockdown THP-1 (ECSITKD THP-1) cells exhibited severe impairments in NF-κB activity, cytokine productions, and NF-κB-dependent gene expressions, whereas those were dramatically restored by re-introduction of wild type (wt) ECSIT gene. Interestingly, ECSIT mutants, in which lack a specific interacting domain for either TAK1 or TRAF6, could not restore these activities. Moreover, no significant changes in both NF-κB activity and cytokine productions induced by TLR4 could be seen in TAK1KD or TRAF6KD THP-1 cells transduced by wt ECSIT, strongly suggesting the essential requirement of TAK1-ECSIT-TRAF6 complex in TLR4 signaling. Taken together, our data demonstrate that the ECSIT complex, including TAK1 and TRAF6, plays a pivotal role in TLR4-mediated signals to activate NF-κB.
    Journal of Biological Chemistry 11/2014; 289(51). DOI:10.1074/jbc.M114.597187 · 4.60 Impact Factor
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    ABSTRACT: Recent evidence shows that evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitinated, and contributes to bactericidal activity during Toll-like receptor (TLR) signaling. Here, we first report a new regulatory role for ECSIT in TLR4 signaling. On TLR4 stimulation, endogenous ECSIT forms a molecular complex if p65/p50 NF- Κ: Bs. Our biochemical studies show that ECSIT specifically interacted with p65/p50 NF- Κ: Bs, which colocalized in the nucleus. Interestingly, these effects were critically dependent on ubiquitination of the ECSIT lysine (K) 372 residue. K372A mutant ECSIT did not interact with p65/p50 NF- Κ: Bs, and markedly attenuated nuclear colocalization. Additionally, ECSIT-knockdown THP-1 cells could not activate NF- Κ: B DNA-binding activities of p65 and p50, production of proinflammatory cytokines, and NF- Κ: B-dependent gene expression in response to TLR4 stimulation. However, these activities were markedly restored by expressing the wild-type ECSIT protein but not the K372A mutant ECSIT protein. These date strongly suggest that the ubiquitination of ECSIT might have the regulation of NF- Κ: B activity in TLR4 signaling.
    Molecular Biology of the Cell 10/2014; 26(1). DOI:10.1091/mbc.E14-08-1277 · 4.55 Impact Factor
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    Sae Mi Wi, Ki-Young Lee
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    ABSTRACT: It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-α1 phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA laddering, and caspase activity in human myeloid cell. AMPK activation is therefore implicated in apoptosis. However, AMPK-α1-knockdown THP-1 cells are more sensitive to apoptosis than control THP-1 cells are, suggesting that the apoptosis is AMPK-independent. Low doses of AICAR induce cell proliferation, whereas high doses of AICAR suppress cell proliferation. Moreover, these effects are significantly correlated with the downregulation of intracellular ROS, strongly suggesting that AICAR-induced apoptosis is critically associated with the inhibition of NADPH oxidase by AICAR. Collectively, our results demonstrate that in AICAR-induced apoptosis, intracellular ROS levels are far more relevant than AMPK activation.
    Immune Network 10/2014; 14(5):241-8. DOI:10.4110/in.2014.14.5.241
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    ABSTRACT: HP1492 is a NifU-like protein of Helicobacter pylori (H. pylori) and plays a role as a scaffold which transfer Fe-S cluster to Fe-S proteins like Ferredoxin. To understand how to bind to iron ion or iron-sulfur cluster, HP1492 was expressed and purified in Escherichia coli (E. coli). From the NMR measurement, we could carry out the sequence specific backbone resonance assignment of HP1492. Approximately 91% of all resonances could be assigned unambiguously. By analyzing results of CSI and TALOS from NMR data, we could predict the secondary structure of HP1492, which consists of three -helices and three -sheets. This study is an essential step towards the structural characterization of HP1492.
    12/2013; 17(2). DOI:10.6564/JKMRS.2013.17.2.105
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    ABSTRACT: Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is key regulator in the signals transduced by pro-inflammatory cytokines and toll-like receptors (TLRs). The regulatory mechanism of TAK1 in response to various tissue types and stimuli remains incompletely understood. Here, we show that ribosomal S6 kinase 1 (S6K1) negatively regulates TLR-mediated signals by inhibiting TAK1 activity. S6K1 overexpression causes a marked reduction in NF-κB and AP-1 activity induced by TLR2 or TLR4 stimulation. In contrast, S6K1(-/-) and S6K1-knockdown cells display enhanced production of inflammatory cytokines. Moreover, S6K1(-/-) mice exhibit decreased survival in response to challenge of LPS. We found that S6K1 inhibits TAK1 kinase activity by interfering with the interaction between TAK1 and TAB1, a key regulator protein for TAK1 catalytic function. Upon stimulation with TLR ligands, S6K1 deficiency causes a marked increase in TAK1 kinase activity that in turn induces a substantial enhancement of NF-κB-dependent gene expression, indicating that S6K1 is negatively involved in the TLR signaling pathway by the inhibition of TAK1 activity. Our findings contribute to understanding the molecular pathogenesis of the impaired immune responses seen in type 2 diabetes where S6K1 plays a key role in driving both insulin resistance and modulating TLR signaling.
    Molecular and Cellular Biology 11/2013; DOI:10.1128/MCB.01225-13 · 5.04 Impact Factor
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    ABSTRACT: Salt-inducible kinases (SIKs) are a family of related serine-threonine kinases and are involved in controlling various metabolisms such as liver glucose homeostasis, hepatic lipogenesis, steroidogenesis, and adipogenesis. Here we investigated the regulatory role of SIK proteins in Toll-like receptor 4 (TLR4)-mediated signaling. Overexpression of SIK1 and SIK3, but not SIK2, significantly inhibited nuclear factor-κB activity in response to lipopolysaccharide stimulation and affected the expression of proinflammatory cytokines. In contrast, both SIK1(KD) and SIK3(KD) Raw 264.7 cells exhibit dramatic elevations of nuclear factor-κB activation and activations of downstream signaling molecules, such as TGF-β-activated kinase 1, p38, and c-Jun N-terminal kinase, in response to TLR4 stimulation, indicating that SIK1 and SIK3 are negatively involved in the TLR4-mediated signaling. Through biochemical studies, we found that SIK1 and SIK3 interact with TGF-β-activated kinase 1-binding protein 2 (TAB2), and interrupt the functional complex of TAB2-TNF receptor-associated factor 6 (TRAF6). Interestingly, the molecular interruption is induced to suppress the ubiquitination of TRAF6 in response to TLR4 stimulation. These result suggest that SIK1 and SIK3 negatively regulate TLR4-mediated signaling through the interruption of TAB2-TRAF6 complex and thereby the inhibition of ubiquitination of TRAF6. The present findings can be useful for a better understanding of multilevel interactions between the metabolic and immune systems.
    Molecular Endocrinology 09/2013; 27(11). DOI:10.1210/me.2013-1240 · 4.20 Impact Factor
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    ABSTRACT: SAV0506 is an 87 residue hypothetical protein from Staphylococcus aureus strain Mu50 and also predicted to have similar function to ribosome associated heat shock protein, Hsp 15. Hsp15 is thought to be involved in the repair mechanism of erroneously produced 50S ribosome subunit. In this report, we present the sequence specific backbone resonance assignment of SAV0506. About 82.5% of all resonances could be assigned unambiguously. By analyzing deviations of the and chemical shift values, we could predict the secondary structure of SAV0506. This study is an essential step towards the structural characterization of SAV0506.
    06/2013; 17(1). DOI:10.6564/JKMRS.2013.17.1.054
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    ABSTRACT: Complex I (NADH-quinone oxidoreductase) is an enzyme that catalyzes the initial electron transfer from nicotinamide adenine dinucleotide (NADH) to flavin mononucleotide (FMN) bound at the tip of the hydrophilic domain of complex I. The electron flow into complex I is coupled to the generation of a proton gradient across the membrane that is essential for the synthesis of ATP. However, Helicobacter pylori has an unusual complex I that lacks typical NQO1 and NQO2 subunits, both of which are generally included in the NADH dehydrogenase domain of complex I. Here, we determined the solution structure of HP1264, one of the unusual subunits of complex I from H. pylori, which is located in place of NQO2, by three-dimensional nuclear magnetic resonance (NMR) spectroscopy and revealed that HP1264 can bind to FMN through UV-visible, fluorescence, and NMR titration experiments. This result suggests that FMN-bound HP1264 could be involved in the initial electron transfer step of complex I. In addition, HP1264 is structurally most similar to Escherichia coli TusA, which belongs to the SirA-like superfamily having an IF3-like fold in the SCOP database, implying that HP1264 adopts a novel fold for FMN binding. On the basis of the NMR titration data, we propose the candidate residues Ile32, Met34, Leu58, Trp68, and Val71 of HP1264 for the interaction with FMN. Notably, these residues are not conserved in the FMN binding site of any other flavoproteins with known structure. This study of the relationship between the structure and FMN binding property of HP1264 will contribute to improving our understanding of flavoprotein structure and the electron transfer mechanism of complex I.
    Biochemistry 03/2013; 52(9):1583-93. DOI:10.1021/bi301714a · 3.19 Impact Factor
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    ABSTRACT: Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPKα1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPKα1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPKα1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma.
    Biochemical pharmacology 10/2012; 84(12). DOI:10.1016/j.bcp.2012.09.025 · 4.65 Impact Factor
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    ABSTRACT: BACKGROUND: Antioxidants have been suggested to alleviate the pathophysiological features of asthma, and grape seed proanthocyanidin extract (GSPE) has been reported to have powerful antioxidant activity. PURPOSE: This study was performed to determine whether GSPE has a therapeutic effect on allergic airway inflammation in both acute and chronic murine model of asthma. METHODS: Acute asthma model was generated by intraperitoneal sensitization of ovalbumin (OVA) with alum followed by aerosolized OVA challenges, whereas chronic asthma model was induced by repeated intranasal challenges of OVA with fungal protease twice a week for 8 weeks. GSPE was administered by either intraperitoneal injection or oral gavage before OVA challenges. Airway hyperresponsiveness (AHR) was measured, and airway inflammation was evaluated by bronchoalveolar lavage (BAL) fluid analysis and histopathological examination of lung tissue. Lung tissue levels of various cytokines, chemokines, and growth factors were analyzed by quantitative polymerase chain reaction and ELISA. Glutathione assay was done to measure oxidative burden in lung tissue. RESULTS: Compared to untreated asthmatic mice, mice treated with GSPE showed significantly reduced AHR, decreased inflammatory cells in the BAL fluid, reduced lung inflammation, and decreased IL-4, IL-5, IL-13, and eotaxin-1 expression in both acute and chronic asthma models. Moreover, airway subepithelial fibrosis was reduced in the lung tissue of GSPE-treated chronic asthmatic mice compared to untreated asthmatic mice. Reduced to oxidized glutathione (GSH/GSSG) ratio was increased after GSPE treatment in acute asthmatic lung tissue. CONCLUSION: GSPE effectively suppressed inflammation in both acute and chronic mouse models of asthma, suggesting a potential role of GSPE as a therapeutic agent for asthma.
    Journal of Clinical Immunology 07/2012; 32(6). DOI:10.1007/s10875-012-9742-8 · 2.65 Impact Factor
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    ABSTRACT: Cell adhesion molecules play a crucial role in fundamental biological processes via regulating cell-cell interactions. Nerve injury induced protein1 (Ninjurin1) is a novel adhesion protein that has no significant homology with other known cell adhesion molecules. Here we present the assignment of an 81 aa construct for human Ninjurin1 Extracellular N-Terminal (ENT) domain, which comprises the critical adhesion domain.
    Biomolecular NMR Assignments 06/2012; DOI:10.1007/s12104-012-9400-3 · 0.82 Impact Factor
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    ABSTRACT: Polycations such as polybrene (PB) are routinely used for most retroviral vector-mediated gene transfer studies because they can increase the infectivity of retroviruses. However, it was not systematically determined if addition of the polycation is an essential prerequisite for all retroviral transductions. To test this, we measured the effects of the polycation on transduction efficiency using various combinations of target cells and pseudotyped viral envelope (Env) proteins. Here, we show polycations do not always increase retroviral transduction efficiency and that their enhancing effect depends on both the type of target cells and Env proteins. The findings presented here also suggest that high transduction rates can be achieved in primary neural stem cells in vitro and in vivo by choosing an appropriate Env protein for pseudotyping without using polycations which are potentially toxic to primary cells and may change the intrinsic characteristics of cells.
    Neurochemistry International 03/2012; 60(8):846-51. DOI:10.1016/j.neuint.2012.02.033 · 2.65 Impact Factor
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    ABSTRACT: Sustained increase in [Ca(2+)](c) (Δ[Ca(2+)](c)) is a critical early signal from T-cell receptor (TCR/CD3). In general, Ca(2+)-release activated Ca(2+) channels (CRAC) are responsible for the Ca(2+) influx and Δ[Ca(2+)](c) after TCR/CD3 stimulation. However, T cells also express Ca(2+)-permeable nonselective cation channels such as TRPM2 and TRPC. Gd(3+) is a relatively selective blocker for CRAC at micromolar concentrations. Here, Jurkat T cells were used to investigate the Gd(3+)-resistant Ca(2+) influx (Δ[Ca(2+)](c,Gd)) induced by concanavalin A (ConA, 1 μg/ml), a widely used mitogenic agent for T cells, or by anti-CD3 Ab (αCD3). αCD3-induced Δ[Ca(2+)](c) was partly (~60%) inhibited by 1 μM Gd(3+) while thapsigargin-induced Δ[Ca(2+)] was almost completely abolished. ConA-induced Δ[Ca(2+)] was mostly inhibited by 1 μM Gd(3+) during the early phase (<30 s of ConA application) and became resistant during the late phase (>2 min). Induction of Δ[Ca(2+)](c,Gd) by αCD3 and ConA was inhibited by 2-aminoethoxydiphenyl borate (2-APB) and by N-(p-amylcinnamoyl) anthranilic acid, indicating that TRPM2 and TRPC are involved in this process. Treatment with Pyr-3, a TRPC3-specific inhibitor, potently suppressed Δ[Ca(2+)](c,Gd) by αCD3 (IC(50), 0.16 μM). Patch clamp experiments demonstrated that the TRPM2 channels were activated by ConA, and the TRPC-like channels were activated by αCD3. Our present study suggests that TRPM2 and TRPC3 are activated by ConA and TCR/CD3, respectively, in Jurkat T cells and are responsible for the induction of Δ[Ca(2+)](c,Gd).
    Pflügers Archiv - European Journal of Physiology 02/2012; 463(2):309-18. DOI:10.1007/s00424-011-1039-x · 3.07 Impact Factor
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    ABSTRACT: Oxidative stress is involved in the pathogenesis of asthma, and peroxiredoxins (PRDX) may be critical in controlling intracellular oxidative stress. The aim of this study was to evaluate expressions of PRDX and their hyperoxidized forms in asthmatic individuals. The levels of expression of PRDX1, PRDX2, PRDX3, and PRDX6 and their hyperoxidized forms (PRDX-SO(3)) were measured in PBMCs from asthma patients and control subjects. In addition, cells from these subjects were treated with hydrogen peroxide (H(2)O(2)) and their intracellular concentrations of reactive oxygen species (ROS) were measured. The ratios of hyperoxidized to total PRDX (PRDX-SO(3/)PRDX) in PBMCs were significantly higher in asthma patients than in normal subjects and were correlated with disease severity, with the highest ratio seen in patients with severe asthma. Furthermore, H(2)O(2) treatment of PBMCs, particularly lymphocytes, increased intracellular ROS concentrations with greater and more persistent increases observed in cells from asthmatic than from control subjects. Hyperoxidation of PRDX may serve as a biomarker of asthma severity and may predict enhanced susceptibility to oxidative stress load in PBMCs of asthmatics.
    Life sciences 01/2012; 90(13-14):502-8. DOI:10.1016/j.lfs.2012.01.003 · 2.30 Impact Factor
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    ABSTRACT: VapD-like virulence-associated proteins have been found in many organisms, but little is known about this protein family including the 3D structure of these proteins. Recently, a relationship between the Cas2 family of ribonucleases associated with the CRISPR system of microbial immunity and VapD was suggested. Here, we show for the first time the structure of a member of the VapD family and present a relationship of VapD with Cas2 family and toxin-antitoxin (TA) systems. The crystal structure of HP0315 from Helicobacter pylori was solved at a resolution of 2.8 Å. The structure of HP0315, which has a modified ferredoxin-like fold, is very similar to that of the Cas2 family. Like Cas2 proteins, HP0315 shows endoribonuclease activity. HP0315-cleaved mRNA, mainly before A and G nucleotides preferentially, which means that HP0315 has purine-specific endoribonuclease activity. Mutagenesis studies of HP0315 revealed that D7, L13, S43 and D76 residues are important for RNase activity, in contrast, to the Cas2 family. HP0315 is arranged as an operon with HP0316, which was found to be an antitoxin-related protein. However, HP0315 is not a component of the TA system. Thus, HP0315 may be an evolutionary intermediate which does not belong to either the Cas2 family or TA system.
    Nucleic Acids Research 01/2012; 40(9):4216-28. DOI:10.1093/nar/gkr1305 · 8.81 Impact Factor
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    ABSTRACT: Unexplained chronic cough is a common condition without specific causes. A hyperreactivity of the cough reflex has been suggested as a mechanism for inducing chronic cough. We hypothesized that nitrosative stress in the upper airway might play a role in cough hypersensitivity by causing neurochemical abnormalities. Fifty-one patients with unexplained chronic cough and 27 controls were enrolled. A capsaicin cough provocation test was performed to determine cough sensitivity. Nitrosative stress in the upper airway was assessed by quantifying 3-nitrotyrosine (3-NT) immunostaining in nasal epithelial cells (NECs) and measuring nasal nitric oxide (nNO). The effect of NO on airway epithelium was investigated by measuring the levels of substance P (SP) in nasal lavage fluid and evaluating SP expression in airway epithelial cells. Based on the results of the capsaicin test, patients were divided into two groups: a cough hypersensitivity (CHS) group and a normal cough sensitivity (NCS) group. The levels of 3-NT immunoreactivity in NECs were significantly higher in CHS (49 ± 2.9%) than in NCS (27 ± 3.3%) and controls (12 ± 1.6%), a pattern that was also reflected in the values of nNO (350 ± 43, 215 ± 23, and 138 ± 23 ppb in CHS, NCS, and controls, respectively). SP concentration was also elevated in nasal lavage fluids from CHS (746 ± 28 pg/mL) compared with that from NCS (624 ± 40 pg/mL) and controls (526 ± 41 pg/mL). SP expression in airway epithelial cells was greatly enhanced by exposure to NO donor, which was attenuated by pretreatment with either NO scavenger or NO synthase inhibitor. Increased nitrosative stress in the upper airway may play a role in the pathogenesis of unexplained chronic cough with CHS through enhanced secretion of SP.
    American Journal of Rhinology and Allergy 01/2012; 26(1):e10-4. DOI:10.2500/ajra.2012.26.3730 · 2.18 Impact Factor
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    ABSTRACT: Mitogen-activated protein kinase kinase kinases (MAP3Ks) are activated by a wide spectrum of extracellular stimuli and are involved in various cellular events including proinflammatory and oxidative damage response through activations of two specific transcription factors, nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Although members of the MAP3K family have both overlapping and distinct functions, the inter-regulatory mechanism of MAP3Ks remains largely unknown. In this study we demonstrated that transforming growth factor-β-activated kinase 1 (TAK1)-TAK1-binding protein 1 (TAB1) complex negatively regulates ASK1-mediated signaling, and TAB2 reciprocally regulates TAK1-induced NF-κB and apoptosis signal-regulating kinase 1 (ASK1)-mediated AP-1 activations through the TAK1-TAB2 interaction and the interferences of TAK1-ASK1 interaction. TAK1 interacted with the N or C terminus of ASK1 through the C-terminal TAB2 binding domain of TAK1, with resultant inhibition of ASK1-induced AP-1 activation. Interestingly, the interaction between TAK1 and TAB2 significantly attenuated the ASK1-TAK1 interaction through the competitive interaction with ASK1 to TAK1 and resulted in the activations of TAK1-induced activations of NF-κB and AP-1. More interestingly, H(2)O(2)- and TNF-α-induced apoptosis in TAK1-deficient mouse embryo fibroblast cells were dramatically enhanced by overexpression of ASK1, whereas the apoptosis was markedly inhibited by the overexpression of TAK1. Overall, these results demonstrate that TAK1 and its adapter protein, TAB2, reciprocally regulate both TAK1- and ASK1-mediated signaling pathways to direct the activations of NF-κB and AP-1.
    Journal of Biological Chemistry 12/2011; 287(5):3381-91. DOI:10.1074/jbc.M111.317875 · 4.60 Impact Factor
  • Eunna Choi, Ki-Young Lee, Dongwoo Shin
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    ABSTRACT: MgtR is a 30 amino acid peptide that is encoded from the mgtCBR operon. This peptide has recently been demonstrated to interact with the MgtC virulence protein and lead to MgtC degradation. In the present study, we reveal that the MgtA Mg(2+) transporter is another protein under the direct control of the MgtR peptide. Salmonella expresses the MgtA transporter only in Mg(2+) depleted conditions. We determined that the MgtR peptide limits levels of the MgtA protein at low Mg(2+) concentrations. MgtA expression increased in a Salmonella strain lacking MgtR but decreased in a strain overexpressing MgtR. Moreover, we found that the MgtR peptide is necessary for the MgtA protein to be induced at the normal timing upon Mg(2+) starvation. The MgtR peptide did not affect transcription of the mgtA gene but specifically bound to the MgtA transporter in vivo, resembling the features of MgtR-regulated MgtC expression. MgtR-mediated regulation of MgtA expression was biologically significant because the lack of MgtR enhanced Salmonella growth in low Mg(2+).
    Biochemical and Biophysical Research Communications 12/2011; 417(1):318-23. DOI:10.1016/j.bbrc.2011.11.107 · 2.28 Impact Factor

Publication Stats

1k Citations
239.43 Total Impact Points

Institutions

  • 2008–2014
    • Sungkyunkwan University
      • • Department of Molecular and Cell Biology
      • • School of Medicine
      Sŏul, Seoul, South Korea
  • 2009–2013
    • Seoul National University
      • • Research Institute of Pharmaceutical Sciences
      • • College of Pharmacy
      Sŏul, Seoul, South Korea
  • 2006–2008
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2005
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2004–2005
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2002
    • Yonsei University
      • Department of Biotechnology
      Sŏul, Seoul, South Korea
    • Ewha Womans University
      Sŏul, Seoul, South Korea