Mantle cell lymphoma: transcriptional regulation by microRNAs.
AuthorsDi Lisio L, Gómez-López G, Sánchez-Beato M, Gómez-Abad C, RodrÃguez ME, Villuendas R, Ferreira BI, Carro A, Rico D, Mollejo M, MartÃnez MA, Menárguez J, DÃaz-Alderete A, Gil J, Cigudosa JC, Pisano DG, Piris MA, MartÃnez N,
JournalLeukemia
PubMed ID20485376
Mantle cell lymphoma (MCL) pathogenesis is still partially unexplained. We investigate the importance of microRNA (miRNA) expression as an additional feature that influences MCL pathway deregulation and may be useful for predicting patient outcome. Twenty-three MCL samples, eight cell lines and appropriate controls were screened for their miRNAs and gene ... More
GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9.
AuthorsOstman JA, Nassar MA, Wood JN, Baker MD,
JournalJ Physiol
PubMed ID18096591
'Persistent tetrodotoxin-resistant (TTX-r) sodium currents up-regulated by intracellular GTP have been invoked as the site of action of peripheral inflammatory mediators that lower pain thresholds, and ascribed to the Na(V)1.9 sodium channel. Here we describe the properties of a global knock-out of Na(V)1.9 produced by replacing exons 4 and 5 ... More
Functional interaction of the human cytomegalovirus IE2 protein with histone deacetylase 2 in infected human fibroblasts.
AuthorsPark JJ, Kim YE, Pham HT, Kim ET, Chung YH, Ahn JH,
JournalJ Gen Virol
PubMed ID18024889
'In human cytomegalovirus (HCMV)-infected cells, the 86 kDa immediate-early (IE) 2 protein plays a key role in transactivating downstream viral genes. Recently, IE2 has been shown to interact with histone deacetylase 1 (HDAC1) and HDAC3. HDAC1 recruited by IE2 was required for IE2-mediated autorepression of the major IE (MIE) promoter, ... More
Dose-dependent differential regulation of cytokine secretion from macrophages by fractalkine.
AuthorsMizutani N, Sakurai T, Shibata T, Uchida K, Fujita J, Kawashima R, Kawamura YI, Toyama-Sorimachi N, Imai T, Dohi T,
JournalJ Immunol
PubMed ID18025192
'Although expression of the fractalkine (CX3CL1, FKN) is enhanced in inflamed tissues, it is detected at steady state in various organs such as the intestine, and its receptor CX3CR1 is highly expressed in resident-type dendritic cells and macrophages. We hypothesized that FKN might regulate the inflammatory responses of these cells. ... More
Molecular regulation of matrix extracellular phosphoglycoprotein expression by bone morphogenetic protein-2.
AuthorsCho YD, Yoon WJ, Woo KM, Baek JH, Lee G, Cho JY, Ryoo HM,
JournalJ Biol Chem
PubMed ID19617624
'Matrix extracellular phosphoglycoprotein (MEPE) is mainly expressed in mineralizing tissues, and its C-terminal proteolytic cleavage product is an acidic-serine-asparate-rich-MEPE-associated motif (ASARM) that is a strong regulator of body phosphate metabolism and mineralization. There is sufficient data supporting a role for MEPE protein function in mineralization, however, little is known about ... More
Molecular cloning and characterization of Foxp3 in Atlantic salmon (Salmo salar).
AuthorsZhang Z, Chi H, Niu C, Bøgwald J, Dalmo RA,
JournalFish Shellfish Immunol
PubMed ID21276855
'Foxp3 is a T cell-specific transcription factor and plays a key role in the development of Treg cells and in the immune regulatory process during inflammation. Here we report cloning and characterization of the full-length cDNA of Atlantic salmon Foxp3, which possesses a Forkhead domain, a zinc finger domain and ... More
Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema.
AuthorsRoh GS, Yi CO, Cho YJ, Jeon BT, Nizamudtinova IT, Kim HJ, Kim JH, Oh YM, Huh JW, Lee JH, Hwang YS, Lee SD, Lee JD,
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID20472710
'Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drug''s anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we ... More
Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells.
AuthorsLim JY, Park SH, Jeong CH, Oh JH, Kim SM, Ryu CH, Park SA, Ahn JG, Oh W, Jeun SS, Chang JW,
JournalBMC Biotechnol
PubMed ID20462460
'Mesenchymal stem cells (MSCs) are an attractive source of adult stem cells for therapeutic application in clinical study. Genetic modification of MSCs with beneficial genes makes them more effective for therapeutic use. However, it is difficult to transduce genes into MSCs by common transfection methods, especially nonviral methods. In this ... More
Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts.
AuthorsYe H, Jeong SY, Ghosh MC, Kovtunovych G, Silvestri L, Ortillo D, Uchida N, Tisdale J, Camaschella C, Rouault TA,
JournalJ Clin Invest
PubMed ID20364084
'Glutaredoxin 5 (GLRX5) deficiency has previously been identified as a cause of anemia in a zebrafish model and of sideroblastic anemia in a human patient. Here we report that GLRX5 is essential for iron-sulfur cluster biosynthesis and the maintenance of normal mitochondrial and cytosolic iron homeostasis in human cells. GLRX5, ... More
Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling.
AuthorsKang L, Zhang X, Xie Y, Tu Y, Wang D, Liu Z, Wang ZY,
JournalMol Endocrinol
PubMed ID20197310
'Accumulating evidence suggested that an orphan G protein-coupled receptor (GPR)30, mediates nongenomic responses to estrogen. The present study was performed to investigate the molecular mechanisms underlying GPR30 function. We found that knockdown of GPR30 expression in breast cancer SK-BR-3 cells down-regulated the expression levels of estrogen receptor (ER)-alpha36, a variant ... More
T cell Ig domain and mucin domain 1 engagement on invariant NKT cells in the presence of TCR stimulation enhances IL-4 production but inhibits IFN-gamma production.
AuthorsKim HS, Kim HS, Lee CW, Chung DH,
JournalJ Immunol
PubMed ID20220086
'The T cell Ig domain and mucin domain (TIM)1 protein expressed on the surface of Th2 cells regulates the immune response by modulating cytokine production. However, the functional roles of TIM1 have not been examined in NKT cells. Therefore, we investigated the immunologic effects of TIM1 on NKT cells. We ... More
Genetic analysis of hierarchical regulation for Gata1 and NF-E2 p45 gene expression in megakaryopoiesis.
AuthorsTakayama M, Fujita R, Suzuki M, Okuyama R, Aiba S, Motohashi H, Yamamoto M,
JournalMol Cell Biol
PubMed ID20351175
'GATA1 and NF-E2 p45 are two important regulators of megakaryopoiesis. Whereas GATA1 is known to regulate the p45 gene, details of the GATA1 contribution to the spatiotemporal expression of the p45 gene remain to be elucidated. To clarify the relationship between GATA1 and p45, we performed genetic complementation rescue analysis ... More
Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis.
AuthorsWang CY, Lin YS, Su WC, Chen CL, Lin CF,
JournalMol Biol Cell
PubMed ID19656851
'Annexin A2 is involved in multiple cellular processes, including cell survival, growth, division, and differentiation. A lack of annexin A2 makes cells more sensitive to apoptotic stimuli. Here, we demonstrate a potential mechanism for apoptotic stimuli-induced annexin A2 cleavage, which contributes to cell cycle inhibition and apoptosis. Annexin A2 was ... More
Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q.
AuthorsYoshizaki M, Tazawa A, Kasumi E, Sasawatari S, Itoh K, Dohi T, Sasazuki T, Inaba K, Makrigiannis AP, Toyama-Sorimachi N,
JournalBlood
PubMed ID19528537
'Toll-like receptor (TLR) 9 recognizes unmethylated microorganismal cytosine guanine dinucleotide (CpG) DNA and elicits innate immune responses. However, the regulatory mechanisms of the TLR signaling remain elusive. We recently reported that Ly49Q, an immunoreceptor tyrosine-based inhibitory motif-bearing inhibitory receptor belonging to the natural killer receptor family, is crucial for TLR9-mediated ... More
Phosphorylation of p27Kip1 by Epstein-Barr virus protein kinase induces its degradation through SCFSkp2 ubiquitin ligase actions during viral lytic replication.
AuthorsIwahori S, Murata T, Kudoh A, Sato Y, Nakayama S, Isomura H, Kanda T, Tsurumi T,
JournalJ Biol Chem
PubMed ID19451650
'Epstein-Barr virus (EBV) productive replication occurs in an S-phase-like cellular environment with high cyclin-dependent kinase (CDK) activity. The EBV protein kinase (PK), encoded by the viral BGLF4 gene, is a Ser/Thr protein kinase, which phosphorylates both viral and cellular proteins, modifying the cellular environment for efficient viral productive replication. We ... More
PML-IV functions as a negative regulator of telomerase by interacting with TERT.
AuthorsOh W, Ghim J, Lee EW, Yang MR, Kim ET, Ahn JH, Song J,
JournalJ Cell Sci
PubMed ID19567472
'Maintaining proper telomere length requires the presence of the telomerase enzyme. Here we show that telomerase reverse transcriptase (TERT), a catalytic component of telomerase, is recruited to promyelocytic leukemia (PML) nuclear bodies through its interaction with PML-IV. Treatment of interferon-alpha (IFNalpha) in H1299 cells resulted in the increase of PML ... More
Protective role of autophagy in palmitate-induced INS-1 beta-cell death.
AuthorsChoi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, Kim Y, Jun HS, Lee KW, Kang Y,
JournalEndocrinology
PubMed ID18772242
'Autophagy, a vacuolar degradative pathway, constitutes a stress adaptation that avoids cell death or elicits the alternative cell-death pathway. This study was undertaken to determine whether autophagy is activated in palmitate (PA)-treated beta-cells and, if activated, what the role of autophagy is in the PA-induced beta-cell death. The enhanced formation ... More
MicroRNA-9 modulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium.
AuthorsShibata M, Kurokawa D, Nakao H, Ohmura T, Aizawa S,
JournalJ Neurosci
PubMed ID18842901
'Vertebrate brain hosts a diverse collection of microRNAs, but little is known about their functions in vivo. Here we propose that mouse microRNA-9 (miR-9) targets Foxg1 mRNAs for proper generation of Cajal-Retzius cells in the medial pallium. miR-9 expression is mediolaterally graded, being most intense in the cortical hem; it ... More
Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B cell development.
AuthorsSong R, Kim YW, Koo BK, Jeong HW, Yoon MJ, Yoon KJ, Jun DJ, Im SK, Shin J, Kong MP, Kim KT, Yoon K, Kong YY,
JournalJ Exp Med
PubMed ID18824586
'Notch signaling regulates lineage decisions at multiple stages of lymphocyte development, and Notch activation requires the endocytosis of Notch ligands in the signal-sending cells. Four E3 ubiquitin ligases, Mind bomb (Mib) 1, Mib2, Neuralized (Neur) 1, and Neur2, regulate the Notch ligands to activate Notch signaling, but their roles in ... More
Up-regulation of activating transcription factor-5 suppresses SAP expression to activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus infection and immune disorders.
AuthorsChuang HC, Wang JM, Hsieh WC, Chang Y, Su IJ,
JournalAm J Pathol
PubMed ID18832568
'Hemophagocytic syndrome (HPS) is a fatal, pro-inflammatory cytokine disorder that is associated with viral infections and immune disorders. Previously, we demonstrated that Epstein-Barr virus latent membrane protein-1 (LMP-1) could down-regulate the SAP gene, enhancing Th1 cytokine secretion in T cells and leading to HPS. The exact mechanism of SAP gene ... More
The Boston-type craniosynostosis mutation MSX2 (P148H) results in enhanced susceptibility of MSX2 to ubiquitin-dependent degradation.
AuthorsYoon WJ, Cho YD, Cho KH, Woo KM, Baek JH, Cho JY, Kim GS, Ryoo HM,
JournalJ Biol Chem
PubMed ID18786927
'Boston-type craniosynostosis is caused by a single amino acid substitution, P148H, in the transcription factor MSX2. The increased binding affinity of MSX2 (P148H) to the response element has led many to hypothesize that the substitution is a gain-of-function mutation. However, there have been conflicting reports on the function of MSX2, ... More
Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis.
AuthorsHashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y,
JournalCarcinogenesis
PubMed ID20080834
'Aberrant expression of microRNA (miRNA) has been reported in various cancers. To clarify the role of miRNA in gastric carcinogenesis, we performed miRNA microarray analysis and investigated expression changes of miRNAs in a 5-aza-2''-deoxycytidine (5-aza-CdR)-treated gastric cancer cell line, KATO-III. On microarray analysis, five miRNAs were found to be upregulated ... More
Absence of TRIF Signaling in Lipopolysaccharide-Stimulated Murine Mast Cells.
AuthorsKeck S, Müller I, Fejer G, Savic I, Tchaptchet S, Nielsen PJ, Galanos C, Huber M, Freudenberg MA,
JournalJ Immunol
PubMed ID21441453
'In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-ß (TRIF) signaling, emanate from the LPS receptor TLR4/MD-2. In this study, we show that in murine bone marrow-derived mast cells (BMMCs), only the MyD88-dependent pathway is activated by LPS. The TRIF signaling branch leading both to NF-?B ... More
Functional interaction between BubR1 and securin in an anaphase-promoting complex/cyclosomeCdc20-independent manner.
AuthorsKim HS, Jeon YK, Ha GH, Park HY, Kim YJ, Shin HJ, Lee CG, Chung DH, Lee CW,
JournalCancer Res
PubMed ID19117984
'Activation of the mitotic checkpoint requires the precise timing and spatial organization of mitotic regulatory events, and ensures accurate chromosome segregation. Mitotic checkpoint proteins such as BubR1 and Mad2 bind to Cdc20, and inhibit anaphase-promoting complex/cyclosome(Cdc20)-mediated securin degradation and the onset of anaphase. BubR1 mediates the proper attachment of microtubules ... More
Sphingosylphosphorylcholine stimulates CCL2 production from human umbilical vein endothelial cells.
AuthorsLee HY, Lee SY, Kim SD, Shim JW, Kim HJ, Jung YS, Kwon JY, Baek SH, Chung J, Bae YS,
JournalJ Immunol
PubMed ID21368227
'Sphingosylphosphorylcholine (SPC) is a component of high-density lipoprotein particles. We investigated the functional role of SPC in HUVECs. SPC stimulation induced production of the CCL2 chemokine in a PTX-sensitive G-protein-dependent manner. SPC treatment caused the activation of NF-?B and AP-1, which are essential for SPC-induced CCL2 production, and induced the ... More
Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk.
AuthorsIvashchenko O, Van Veldhoven PP, Brees C, Ho YS, Terlecky SR, Fransen M,
JournalMol Biol Cell
PubMed ID21372177
'Reactive oxygen species (ROS) are at once unsought by-products of metabolism and critical regulators of multiple intracellular signaling cascades. In nonphotosynthetic eukaryotic cells, mitochondria are well-investigated major sites of ROS generation and related signal initiation. Peroxisomes are also capable of ROS generation, but their contribution to cellular oxidation-reduction (redox) balance ... More
Protein kinase C{delta} regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis.
AuthorsPark CH, Choi BH, Jeong MW, Kim S, Kim W, Song YS, Kim KT,
JournalMol Biol Cell
PubMed ID21346188
'Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cd (PKCd) in the regulation of murine VRK1. We show that PKCd ... More
ROCK-mediated contractility, tight junctions and channels contribute to the conversion of a preapical patch into apical surface during isochoric lumen initiation.
AuthorsFerrari A, Veligodskiy A, Berge U, Lucas MS, Kroschewski R,
JournalJ Cell Sci
PubMed ID18946028
'Epithelial cells assemble into three-dimensional aggregates to generate lumen-containing organ substructures. Cells therein contact the extracellular matrix with their basal surface, neighbouring cells with their contact surface and the lumen with their apical surface. We investigated the development of single MDCK cells into aggregates with lumen using quantitative live-cell imaging ... More
Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.
AuthorsBarzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S,
JournalJ Cell Sci
PubMed ID20016067
'Cerebellar granular neuronal precursors (CGNPs) proliferate in response to the mitogenic activity of Sonic hedgehog (Shh), and this proliferation is negatively regulated by activation of cAMP-dependent protein kinase (PKA). In the basal state, the PKA catalytic subunits (C-PKA) are inactive because of their association with the regulatory subunits (R-PKA). As ... More
Consortin, a trans-Golgi network cargo receptor for the plasma membrane targeting and recycling of connexins.
Authorsdel Castillo FJ, Cohen-Salmon M, Charollais A, Caille D, Lampe PD, Chavrier P, Meda P, Petit C,
JournalHum Mol Genet
PubMed ID19864490
'Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. We report here on consortin, a novel integral membrane protein that is predicted to ... More
Circadian amplitude of cryptochrome 1 is modulated by mRNA stability regulation via cytoplasmic hnRNP D oscillation.
AuthorsWoo KC, Ha DC, Lee KH, Kim DY, Kim TD, Kim KT,
JournalMol Cell Biol
PubMed ID19858287
'The mammalian circadian rhythm is observed not only at the suprachiasmatic nucleus, a master pacemaker, but also throughout the peripheral tissues. Its conserved molecular basis has been thought to consist of intracellular transcriptional feedback loops of key clock genes. However, little is known about posttranscriptional regulation of these genes. In ... More
Transcriptional activation of hTERT, the human telomerase reverse transcriptase, by nuclear factor of activated T cells.
AuthorsChebel A, Rouault JP, Urbanowicz I, Baseggio L, Chien WW, Salles G, Ffrench M,
JournalJ Biol Chem
PubMed ID19843528
'Telomerase is essential for telomere maintenance, and its activation is thought to be a critical step in cellular immortalization and tumorigenesis. Human telomerase reverse transcriptase (hTERT) is a major component of telomerase activity. We show here that hTERT is expressed soon after lymphocyte activation and that its expression is inhibited ... More
Bestrophin-1 encodes for the Ca2+-activated anion channel in hippocampal astrocytes.
AuthorsPark H, Oh SJ, Han KS, Woo DH, Park H, Mannaioni G, Traynelis SF, Lee CJ,
JournalJ Neurosci
PubMed ID19828819
'In mammalian brain, neurons and astrocytes are reported to express various chloride and anion channels, but the evidence for functional expression of Ca(2+)-activated anion channel (CAAC) and its molecular identity have been lacking. Here we report electrophysiological evidence for the CAAC expression and its molecular identity by mouse Bestrophin 1 ... More
Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway.
AuthorsZhao B, Chun C, Liu Z, Horswill MA, Pramanik K, Wilkinson GA, Ramchandran R, Miao RQ,
JournalBlood
PubMed ID20813898
'Our previous work has shown that axon guidance gene family Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro. To investigate NogoB-NgBR function in vivo, we cloned the zebrafish ortholog of both genes and studied loss of function in vivo using morpholino antisense ... More
Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells.
AuthorsLee CH, Huang CS, Chen CS, Tu SH, Wang YJ, Chang YJ, Tam KW, Wei PL, Cheng TC, Chu JS, Chen LC, Wu CH, Ho YS,
JournalJ Natl Cancer Inst
PubMed ID20733118
'Large epidemiological cohort studies in the United States have indicated that active and passive smoking are associated with increased breast cancer risk. However, there was no direct evidence of an effect of tobacco carcinogens on the cellular molecules involved in breast tumorigenesis. Reverse transcription-polymerase chain reaction was used to determine ... More
Dephosphorylation-dependent inhibitory activity of juxtanodin on filamentous actin disassembly.
AuthorsMeng J, Xia W, Tang J, Tang BL, Liang F,
JournalJ Biol Chem
PubMed ID20610382
'In the vertebrate central nervous system, maturation of oligodendrocytes is accompanied by a dramatic transformation of cell morphology. Juxtanodin (JN) is an actin cytoskeleton-related oligodendroglial protein that promotes arborization of cultured oligodendrocytes. We performed in vitro and in culture experiments to further elucidate the biochemical effects, molecular interactions, and activity ... More
Role of the specific interaction of UL112-113 p84 with UL44 DNA polymerase processivity factor in promoting DNA replication of human cytomegalovirus.
AuthorsKim YE, Ahn JH,
JournalJ Virol
PubMed ID20538862
'The human cytomegalovirus (HCMV) UL112-113 region encodes four phosphoproteins with common amino termini (p34, p43, p50, and p84) via alternative splicing and is thought to be required for efficient viral DNA replication. We have previously shown that interactions among the four UL112-113 proteins regulate their intranuclear targeting and enable the ... More
hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb alpha via IRES-mediated translation.
AuthorsKim DY, Woo KC, Lee KH, Kim TD, Kim KT,
JournalNucleic Acids Res
PubMed ID20576698
'The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb a functions as a transcriptional repressor, affecting expression patterns of other clock ... More
Purinergic signaling: a fundamental mechanism in neutrophil activation.
AuthorsChen Y, Yao Y, Sumi Y, Li A, To UK, Elkhal A, Inoue Y, Woehrle T, Zhang Q, Hauser C, Junger WG,
JournalSci Signal
PubMed ID20530802
'Efficient activation of neutrophils is a key requirement for effective immune responses. We found that neutrophils released cellular adenosine triphosphate (ATP) in response to exogenous stimuli such as formylated bacterial peptides and inflammatory mediators that activated Fcgamma, interleukin-8, C5a complement, and leukotriene B(4) receptors. Stimulation of the formyl peptide receptor ... More
Activation of ASC induces apoptosis or necrosis, depending on the cell type, and causes tumor eradication.
'The adaptor protein ASC (also called TMS1) links certain NLR proteins (e.g., NLRC4, NLRP3) and caspases. It is involved in the chemosensitivity of tumor cells and inflammation. Here, we found that ASC activation using NLRC4 mimicry or an autoinflammatory disease-associated NLRP3 mutant induced necrosis in COLO205 colon adenocarcinoma cells, but ... More
Ratiometric bimolecular beacons for the sensitive detection of RNA in single living cells.
AuthorsChen AK, Davydenko O, Behlke MA, Tsourkas A,
JournalNucleic Acids Res
PubMed ID20507905
'Numerous studies have utilized molecular beacons (MBs) to image RNA expression in living cells; however, there is growing evidence that the sensitivity of RNA detection is significantly hampered by their propensity to emit false-positive signals. To overcome these limitations, we have developed a new RNA imaging probe called ratiometric bimolecular ... More
Small molecule kinase inhibitor screen identifies polo-like kinase 1 as a target for neuroblastoma tumor-initiating cells.
AuthorsGrinshtein N, Datti A, Fujitani M, Uehling D, Prakesch M, Isaac M, Irwin MS, Wrana JL, Al-Awar R, Kaplan DR,
JournalCancer Res
PubMed ID21303981
'Neuroblastoma (NB) is an often fatal pediatric tumor of neural crest origin. We previously isolated NB tumor-initiating cells (NB TIC) from bone marrow metastases that resemble cancer stem cells and form metastatic NB in immunodeficient animals with as few as ten cells. To identify signaling pathways important for the survival ... More
A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo.
AuthorsLi K, Blum Y, Verma A, Liu Z, Pramanik K, Leigh NR, Chun CZ, Samant GV, Zhao B, Garnaas MK, Horswill MA, Stanhope SA, North PE, Miao RQ, Wilkinson GA, Affolter M, Ramchandran R,
JournalBlood
PubMed ID19880500
'Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS ... More
Regulation of alternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein H.
'Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor. The binding of ligands to membrane-bound RAGE (mRAGE) evokes cellular responses involved in various pathological processes. Previously, we identified a novel soluble form, endogenous secretory RAGE (esRAGE) generated by alternative 5'' splice site selection in intron 9 that leads to ... More
Ifi202, an IFN-inducible candidate gene for lupus susceptibility in NZB/W F1 mice, is a positive regulator for NF-kappaB activation in dendritic cells.
AuthorsYamauchi M, Hashimoto M, Ichiyama K, Yoshida R, Hanada T, Muta T, Komune S, Kobayashi T, Yoshimura A,
JournalInt Immunol
PubMed ID17702989
'Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. The [New Zealand black (NZB) x New Zealand white (NZW)]F1 (BWF1) mouse has been recognized as an important animal model of human SLE. The T(h)1-prone phenotype of BWF1 mice has been shown to ... More
Rho and anillin-dependent control of mDia2 localization and function in cytokinesis.
'Diaphanous-related formin, mDia, is an actin nucleation/polymerization factor functioning downstream of the small GTPase Rho. Although Rho is critically involved in cytokinesis, it remains elusive how Rho effectors and other regulators of cytoskeletons work together to accomplish this process. Here we focused on mDia2, an mDia isoform involved in cytokinesis ... More
TCR-induced activation of Ras proceeds at the plasma membrane and requires palmitoylation of N-Ras.
AuthorsRubio I, Grund S, Song SP, Biskup C, Bandemer S, Fricke M, Förster M, Graziani A, Wittig U, Kliche S,
JournalJ Immunol
PubMed ID20713885
'Ras transmits manifold signals from the TCR at various crossroads in the life of a T cell. For example, selection programs in the thymus or the acquisition of a state of hypo-responsiveness known as anergy are just some of the T cell features known to be controlled by TCR-sparked signals ... More
A nonthiazolidinedione peroxisome proliferator-activated receptor a/? dual agonist CG301360 alleviates insulin resistance and lipid dysregulation in db/db mice.
AuthorsJeong HW, Lee JW, Kim WS, Choe SS, Shin HJ, Lee GY, Shin D, Lee JH, Choi EB, Lee HK, Yon GH, Cho B, Kim HR, Choi SH, Chung YS, Park SB, Chung H, Ro S, Kim JB,
JournalMol Pharmacol
PubMed ID20724462
'Activation of peroxisome proliferator-activated receptors (PPARs) have been implicated in the treatment of metabolic disorders with different mechanisms; PPARa agonists promote fatty acid oxidation and reduce hyperlipidemia, whereas PPAR? agonists regulate lipid redistribution from visceral fat to subcutaneous fat and enhance insulin sensitivity. To achieve combined benefits from activated PPARs ... More
Central region of talin has a unique fold that binds vinculin and actin.
AuthorsGingras AR, Bate N, Goult BT, Patel B, Kopp PM, Emsley J, Barsukov IL, Roberts GC, Critchley DR,
JournalJ Biol Chem
PubMed ID20610383
'Talin is an adaptor protein that couples integrins to F-actin. Structural studies show that the N-terminal talin head contains an atypical FERM domain, whereas the N- and C-terminal parts of the talin rod include a series of a-helical bundles. However, determining the structure of the central part of the rod ... More
KIF5B and KIF3A/KIF3B kinesins drive MT1-MMP surface exposure, CD44 shedding, and extracellular matrix degradation in primary macrophages.
AuthorsWiesner C, Faix J, Himmel M, Bentzien F, Linder S,
JournalBlood
PubMed ID20505159
'The matrix metalloproteinase (MMP) MT1-MMP plays pivotal roles in leukocyte physiology such as monocyte diapedesis, dendritic cell migration, and T-cell homing. MT1-MMP is a surface-anchored ' ... More
Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO.
AuthorsHuh YH, Kim YE, Kim ET, Park JJ, Song MJ, Zhu H, Hayward GS, Ahn JH,
JournalJ Virol
PubMed ID18701593
'The human cytomegalovirus (HCMV) 72-kDa immediate-early 1 (IE1) protein is thought to modulate cellular antiviral functions impacting on promyelocytic leukemia (PML) nuclear bodies and signal transducer and activator of transcription (STAT) signaling. IE1 consists of four distinct regions: an amino-terminal region required for nuclear localization, a large central hydrophobic region ... More
Mind bomb-1 is essential for intraembryonic hematopoiesis in the aortic endothelium and the subaortic patches.
AuthorsYoon MJ, Koo BK, Song R, Jeong HW, Shin J, Kim YW, Kong YY, Suh PG,
JournalMol Cell Biol
PubMed ID18505817
'Intraembryonic hematopoiesis occurs at two different sites, the floor of the aorta and subaortic patches (SAPs) of the para-aortic splanchnopleura (P-Sp)/aorta-gonad-mesonephros (AGM) region. Notch1 and RBP-jkappa are critical for the specification of hematopoietic stem cells (HSCs) in Notch signal-receiving cells. However, the mechanism by which Notch signaling is triggered from ... More
The neurogenesis-controlling factor, Pax6, inhibits proliferation and promotes maturation in murine astrocytes.
AuthorsSakurai K, Osumi N,
JournalJ Neurosci
PubMed ID18448636
'Astrocytes serve various important functions in the CNS, but the molecular mechanisms of their generation and maturation are still enigmatic. Here, we show that Pax6, a key transcription factor that controls neurogenesis, also regulates proliferation, differentiation, and migration of astrocytes in the CNS. We first reveal that Pax6 is expressed ... More
A newly identified CG301269 improves lipid and glucose metabolism without body weight gain through activation of peroxisome proliferator-activated receptor alpha and gamma.
AuthorsJeong HW, Lee JW, Kim WS, Choe SS, Kim KH, Park HS, Shin HJ, Lee GY, Shin D, Lee H, Lee JH, Choi EB, Lee HK, Chung H, Park SB, Park KS, Kim HS, Ro S, Kim JB,
JournalDiabetes
PubMed ID21270261
'Peroxisome proliferator-activated receptor (PPAR)-a/? dual agonists have been developed to alleviate metabolic disorders. However, several PPARa/? dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARa/? dual agonist, CG301269, on metabolic disorders both in vitro ... More
Collagen-induced expression of collagenase-3 by primary chondrocytes is mediated by integrin a1 and discoidin domain receptor 2: a protein kinase C-dependent pathway.
'To investigate whether maintaining the chondrocyte''s native pericellular matrix prevents collagen-induced up-regulation of collagenase-3 (MMP-13) and whether integrin a1 (ITGa1) and/or discoidin domain receptor 2 (DDR2) modulate MMP-13 expression and which signalling pathway plays a role in collagen-stimulated MMP-13 expression. Goat articular chondrocytes and chondrons were cultured on collagen coatings. ... More
The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes.
AuthorsCornfine S, Himmel M, Kopp P, El Azzouzi K, Wiesner C, Krüger M, Rudel T, Linder S,
JournalMol Biol Cell
PubMed ID21119006
'Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, ... More
Sonic Hedgehog-induced proliferation requires specific Ga inhibitory proteins.
AuthorsBarzi M, Kostrz D, Menendez A, Pons S,
JournalJ Biol Chem
PubMed ID21209076
'Proliferation of cerebellar granular neuronal precursors (CGNPs) is mediated by Sonic Hedgehog (Shh), which activates the Patched and Smoothened (Smo) receptor complex. Although its protein sequence suggests that Smo is a G protein coupled receptor (GPCR), the evidence that this receptor utilizes heterotrimeric G proteins as downstream effectors is controversial. ... More
Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation.
AuthorsSliter DA, Aguiar M, Gygi SP, Wojcikiewicz RJ,
JournalJ Biol Chem
PubMed ID21071436
'Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are large, ubiquitously expressed, endoplasmic reticulum membrane proteins that form tetrameric IP(3) and Ca(2+)-gated Ca(2+) channels. Endogenous IP(3)Rs provide very appealing tools for studying the ubiquitin-proteasome pathway in intact mammalian cells because, upon activation, they are rapidly ubiquitinated and degraded. Using mass spectrometry, we previously ... More
Arxes: retrotransposed genes required for adipogenesis.
AuthorsProkesch A, Bogner-Strauss JG, Hackl H, Rieder D, Neuhold C, Walenta E, Krogsdam A, Scheideler M, Papak C, Wong WC, Vinson C, Eisenhaber F, Trajanoski Z,
JournalNucleic Acids Res
PubMed ID21177646
'Retrotransposed sequences arise from messenger RNAs (mRNAs) that have been reinserted into genomic DNA by reverse transcription. Usually, these sequences are embedded in dormant regions, collect missense mutations over time and constitute processed, nonfunctional pseudogenes. There are thousands of processed pseudogenes in the mouse and human genome. Here, we report ... More
Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation.
AuthorsKim KS, Choi HW, Yoon HE, Kim IY,
JournalJ Biol Chem
PubMed ID20952384
'Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes ... More
Zona occludens proteins modulate podosome formation and function.
AuthorsKremerskothen J, Stölting M, Wiesner C, Korb-Pap A, van Vliet V, Linder S, Huber TB, Rottiers P, Reuzeau E, Genot E, Pavenstädt H,
JournalFASEB J
PubMed ID20930113
'Podosomes are highly dynamic structures that are involved in cell adhesion and extracellular matrix remodeling. They present as intracellular columns composed of an actin-rich core region and a surrounding ring-like structure containing focal adhesion proteins, actin binders as well as cell signaling molecules. A key player in podosome biogenesis is ... More
NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
AuthorsIyama T, Abolhassani N, Tsuchimoto D, Nonaka M, Nakabeppu Y,
JournalNucleic Acids Res
PubMed ID20385596
'Nucleotides function in a variety of biological reactions; however, they can undergo various chemical modifications. Such modified nucleotides may be toxic to cells if not eliminated from the nucleotide pools. We performed a screen for modified-nucleotide binding proteins and identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein ... More
TORC2, a coactivator of cAMP-response element-binding protein, promotes Epstein-Barr virus reactivation from latency through interaction with viral BZLF1 protein.
AuthorsMurata T, Sato Y, Nakayama S, Kudoh A, Iwahori S, Isomura H, Tajima M, Hishiki T, Ohshima T, Hijikata M, Shimotohno K, Tsurumi T,
JournalJ Biol Chem
PubMed ID19164291
'Reactivation of the Epstein-Barr virus from latency is dependent on expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical inducers such as 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. We found here that Transducer of Regulated cAMP-response Element-binding Protein ... More
ADAMTS1 is a unique hypoxic early response gene expressed by endothelial cells.
AuthorsHatipoglu OF, Hirohata S, Cilek MZ, Ogawa H, Miyoshi T, Obika M, Demircan K, Shinohata R, Kusachi S, Ninomiya Y,
JournalJ Biol Chem
PubMed ID19349275
'ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is a member of the matrix metalloproteinase family. We have previously reported that ADAMTS1 was strongly expressed in myocardial infarction. In this study, we investigated whether hypoxia induced ADAMTS1 and investigated its regulatory mechanism. In hypoxia, the expression level of ADAMTS1 ... More
AuthorsHuang WC, Lin YS, Chen CL, Wang CY, Chiu WH, Lin CF,
JournalJ Pharmacol Exp Ther
PubMed ID19188482
'Glycogen synthase kinase (GSK)-3beta may modulate endoplasmic reticulum (ER) stress-induced apoptosis; however, the mechanism remains unclear. Our data showed that human monocytic leukemia/lymphoma U937 and acute myeloid leukemia HL-60, but not chronic myeloid leukemia K562, cells were susceptible to apoptosis induced by ER stressor tunicamycin, a protein glycosylation inhibitor. Tunicamycin ... More
Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN.
AuthorsWang SK, Liang PH, Astronomo RD, Hsu TL, Hsieh SL, Burton DR, Wong CH,
JournalProc Natl Acad Sci U S A
PubMed ID18310320
'It is widely accepted that the heavily glycosylated glycoprotein gp120 on the surface of HIV-1 shields peptide epitopes from recognition by the immune system and may promote infection in vivo by interaction with dendritic cells and transport to tissue rich in CD4(+) T cells such as lymph nodes. A conserved ... More
Multiple mechanisms downstream of TLR-4 stimulation allow expression of NKG2D ligands to facilitate macrophage/NK cell crosstalk.
AuthorsEissmann P, Evans JH, Mehrabi M, Rose EL, Nedvetzki S, Davis DM,
JournalJ Immunol
PubMed ID20488792
The activating receptor NKG2D recognizes proteins that are not normally expressed at the surface of most cells but are expressed during a cellular
Aberrant expression of cyclin a correlates with morphogenesis of reed-sternberg cells in Hodgkin lymphoma.
AuthorsChang KC, Chang Y, Jones D, Su IJ,
JournalAm J Clin Pathol
PubMed ID19864233
Reed-Sternberg (RS) cells represent a histopathologic hallmark for Hodgkin lymphoma (HL). Viral proteins may induce aberrant expression of cyclin A and lead to multinucleation in virus-infected cells. We investigated whether Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) and cyclin A are involved in the morphogenesis of RS cells. We immunohistochemically ... More
Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1.
AuthorsTibelius A, Marhold J, Zentgraf H, Heilig CE, Neitzel H, Ducommun B, Rauch A, Ho AD, Bartek J, Krämer A,
JournalJ Cell Biol
PubMed ID19546241
Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life. Although primary microcephaly can be caused by mutations in microcephalin (MCPH1), cells from patients with Seckel syndrome and MOPD II harbor ... More
An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.
AuthorsBrailoiu E, Rahman T, Churamani D, Prole DL, Brailoiu GC, Hooper R, Taylor CW, Patel S,
JournalJ Biol Chem
PubMed ID20880839
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca(2+) release from acidic organelles via two-pore channels (TPCs). It has been difficult to resolve this trigger event from its amplification via endoplasmic reticulum Ca(2+) stores, fuelling speculation that archetypal intracellular Ca(2+) channels are the primary targets ... More
CIIA is a novel regulator of detachment-induced cell death.
AuthorsKim KJ, Yu JW, Hwang HS, Choi EJ,
JournalCancer Res
PubMed ID20670956
Detachment-induced cell death, or anoikis, is a type of apoptosis that occurs when epithelial cells lose their attachment to the extracellular matrix. Anoikis serves as a physiologic barrier to metastasis. Deviation from the tightly regulated mechanism of detachment-induced cell death might result in progression to metastatic cancer. Here, we investigated ... More
Differential effects of cytohesins 2 and 3 on beta1 integrin recycling.
AuthorsOh SJ, Santy LC,
JournalJ Biol Chem
PubMed ID20223830
ADP-ribosylation actor 6 (ARF6) regulates the endocytosis and recycling of a variety of proteins and also promotes peripheral actin rearrangements and cell motility. ARF6 is activated by a large number of guanine nucleotide exchange factors, which likely regulate ARF6 at different locations and during different processes. In this study we ... More
Gonadotropin-Releasing Hormone Induces miR-132 and miR-212 to Regulate Cellular Morphology and Migration in Immortalized L{beta}T2 Pituitary Gonadotrope Cells.
AuthorsGodoy J, Nishimura M, Webster NJ,
JournalMol Endocrinol
PubMed ID21372146
GnRH is central to the regulation of reproductive function. It acts on pituitary gonadotropes to stimulate LH and FSH synthesis and secretion. We had previously presented evidence for translational control of LHß synthesis; therefore we investigated whether micro-RNAs might play a role in GnRH regulation in LßT2 cells. We show ... More
PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans.
AuthorsHanazawa M, Yonetani M, Sugimoto A,
JournalJ Cell Biol
PubMed ID21402787
Germ granules are germ lineage-specific ribonucleoprotein (RNP) complexes, but how they are assembled and specifically segregated to germ lineage cells remains unclear. Here, we show that the PGL proteins PGL-1 and PGL-3 serve as the scaffold for germ granule formation in Caenorhabditis elegans. Using cultured mammalian cells, we found that ... More
Endogenously expressed matrix protein M1 and nucleoprotein of influenza A are efficiently presented by class I and class II major histocompatibility complexes.
AuthorsDoucet JD, Forget MA, Grange C, Rouxel RN, Arbour N, von Messling V, Lapointe R,
JournalJ Gen Virol
PubMed ID21307226
Current influenza vaccines containing primarily hypervariable haemagglutinin and neuraminidase proteins must be prepared against frequent new antigenic variants. Therefore, there is an ongoing effort to develop influenza vaccines that also elicit strong and sustained cytotoxic responses against highly conserved determinants such as the matrix (M1) protein and nucleoprotein (NP). However, ... More
N-linked glycans are thought to protect class II major histocompatibility complex (MHC) molecules (MHCII) from proteolytic cleavage and assist in arranging proteins within the immune synapse, but were not thought to directly participate in antigen presentation. Here, we report that antigen-presenting cells (APCs) lacking native complex N-glycans showed reduced MHCII ... More
Overexpression of IL-32{alpha} Increases Natural Killer Cell-mediated Killing through Up-regulation of Fas and UL16-binding protein 2 (ULBP2) Expression in Human Chronic Myeloid Leukemia Cells.
AuthorsCheon S, Lee JH, Park S, Bang SI, Lee WJ, Yoon DY, Yoon SS, Kim T, Min H, Cho BJ, Lee HJ, Lee KW, Jeong SH, Park H, Cho D,
JournalJ Biol Chem
PubMed ID21321117
IL-32 was recently identified as a proinflammatory cytokine that is induced by IL-18 in natural killer (NK) cells and is highly correlated with inflammatory disorders. However, the relationship between IL-32 and tumor progression is still unknown. In this study, we investigated whether overexpression of IL-32 affects susceptibility of chronic myeloid ... More
SIRT1 contributes to telomere maintenance and augments global homologous recombination.
AuthorsPalacios JA, Herranz D, De Bonis ML, Velasco S, Serrano M, Blasco MA,
JournalJ Cell Biol
PubMed ID21187328
Yeast Sir2 deacetylase is a component of the silent information regulator (SIR) complex encompassing Sir2/Sir3/Sir4. Sir2 is recruited to telomeres through Rap1, and this complex spreads into subtelomeric DNA via histone deacetylation. However, potential functions at telomeres for SIRT1, the mammalian orthologue of yeast Sir2, are less clear. We studied ... More
Nucleoredoxin sustains Wnt/ß-catenin signaling by retaining a pool of inactive dishevelled protein.
AuthorsFunato Y, Terabayashi T, Sakamoto R, Okuzaki D, Ichise H, Nojima H, Yoshida N, Miki H,
JournalCurr Biol
PubMed ID20970343
Overexpression of Dishevelled (Dvl), an essential component of the Wnt signaling pathway, is frequently associated with tumors, and thus the Dvl protein level must be tightly controlled to sustain Wnt signaling without causing tumors. Kelch-like 12 (KLHL12) targets Dvl for ubiquitination and degradation, suggesting its potential importance in avoiding aberrant ... More
Activation of AID by human T-cell leukemia virus Tax oncoprotein and the possible role of its constitutive expression in ATL genesis.
AuthorsIshikawa C, Nakachi S, Senba M, Sugai M, Mori N,
JournalCarcinogenesis
PubMed ID20974684
Adult T-cell leukemia (ATL) is a T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). Mutations of tumor suppressor genes have been described in ATL. Although Tax, a product of HTLV-1, is associated with cellular genetic aberrations, the mechanisms of such association are not fully clear. Activation-induced cytidine ... More
The Opdc missense mutation of Pax2 has a milder than loss-of-function phenotype.
AuthorsCross SH, McKie L, West K, Coghill EL, Favor J, Bhattacharya S, Brown SD, Jackson IJ,
JournalHum Mol Genet
PubMed ID20943750
Renal-coloboma syndrome, also known as papillorenal syndrome, is an autosomal dominant human disorder in which optic disc coloboma is associated with kidney abnormalities. Mutations in the paired domain transcription factor PAX2 have been found to be the underlying cause of this disease. Disease severity varies between patients, and in some ... More
A hidden incoherent switch regulates RCAN1 in the calcineurin-NFAT signaling network.
AuthorsShin SY, Yang HW, Kim JR, Do Heo W, Cho KH,
JournalJ Cell Sci
PubMed ID21172821
Regulator of calcineurin 1 (RCAN1) is a key regulator of the calcineurin-NFAT signaling network in organisms ranging from yeast to human, but its functional role is still under debate because different roles of RCAN1 have been suggested under various experimental conditions. To elucidate the mechanisms underlying the RCAN1 regulatory system, ... More
The effects of the stromal cell-derived cyclooxygenase-2 metabolite prostaglandin E2 on the proliferation of colon cancer cells.
AuthorsPark SW, Kim HS, Choi MS, Jeong WJ, Heo DS, Kim KH, Sung MW,
JournalJ Pharmacol Exp Ther
PubMed ID21062968
It is well known that tumor-surrounding stromal tissues support tumor development through secreting soluble factors such as various cytokines, chemokines, and growth factors. It has also been suggested that tumor-associated fibroblast and immune cells have a high expression of cyclooxygenase-2 (COX-2) and produce and secrete several prostaglandins (PGs) to adjacent ... More
BLT2 Is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines.
AuthorsCho KJ, Seo JM, Lee MG, Kim JH,
JournalJ Immunol
PubMed ID20952677
Mast cells are effector cells that mediate the allergic response through Ag stimulation of IgE bound to FceRI. In allergic reactions, cross-linking of the surface receptors for IgE on mast cells results in the synthesis of Th2 cytokines such as IL-4 and IL-13, which are critical for the initiation and ... More
Enhancement of insulin responsiveness by nitric oxide-mediated inactivation of protein-tyrosine phosphatases.
AuthorsHsu MF, Meng TC,
JournalJ Biol Chem
PubMed ID20064934
NO synthesis is a prerequisite for proper insulin sensitivity in insulin-targeted tissues; however, the molecular basis for this process remains unclear. Using a gain-of-function model of endothelial nitric-oxide synthase (eNOS)-transfected COS-7 cells, we have shown a critical role of NO in insulin responsiveness, as evidenced by an NO-dependent increase of ... More
Developmental switch in NF-kappaB signalling required for neurite growth.
AuthorsGavaldà N, Gutierrez H, Davies AM,
JournalDevelopment
PubMed ID19762427
For a given cell type, particular extracellular signals generate characteristic patterns of activity in intracellular signalling networks that lead to distinctive cell-type specific responses. Here, we report the first known occurrence of a developmental switch in the intracellular signalling network required for an identical cellular response to the same extracellular ... More
Sub-cellular trafficking and functionality of 2'-O-methyl and 2'-O-methyl-phosphorothioate molecular beacons.
AuthorsChen AK, Behlke MA, Tsourkas A,
JournalNucleic Acids Res
PubMed ID19820111
Molecular beacons (MBs) have shown great potential for the imaging of RNAs within single living cells; however, the ability to perform accurate measurements of RNA expression can be hampered by false-positives resulting from nonspecific interactions and/or nuclease degradation. These false-positives could potentially be avoided by introducing chemically modified oligonucleotides into ... More
MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein.
AuthorsCharman M, Kennedy BE, Osborne N, Karten B,
JournalJ Lipid Res
PubMed ID19965586
Niemann-Pick Type C (NPC) disease is a fatal, neurodegenerative disorder, caused in most cases by mutations in the late endosomal protein NPC1. A hallmark of NPC disease is endosomal cholesterol accumulation and an impaired cholesterol homeostatic response, which might affect cholesterol transport to mitochondria and, thus, mitochondrial and cellular function. ... More
A novel type of E3 ligase for the Ufm1 conjugation system.
AuthorsTatsumi K, Sou YS, Tada N, Nakamura E, Iemura S, Natsume T, Kang SH, Chung CH, Kasahara M, Kominami E, Yamamoto M, Tanaka K, Komatsu M,
JournalJ Biol Chem
PubMed ID20018847
The ubiquitin fold modifier 1 (Ufm1) is the most recently discovered ubiquitin-like modifier whose conjugation (ufmylation) system is conserved in multicellular organisms. Ufm1 is known to covalently attach with cellular protein(s) via a specific E1-activating enzyme (Uba5) and an E2-conjugating enzyme (Ufc1), but its E3-ligating enzyme(s) as well as the ... More
Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts.
AuthorsMasuda K, Ishikawa Y, Onoyama I, Unno M, de Alborán IM, Nakayama KI, Nakayama K,
JournalOncogene
PubMed ID20023701
The F-box protein Fbxw7 (also known as Fbw7, SEL-10, hCdc4 or hAgo) mediates the ubiquitylation and thereby contributes to the degradation of proteins that positively regulate cell cycle. Conditional ablation of Fbxw7 in mouse embryonic fibroblasts (MEFs) induces cell-cycle arrest accompanied by abnormal accumulation of the intracellular domain of Notch1 ... More
Dysregulation of platelet-derived growth factor beta-receptor expression by DeltaNp73 in neuroblastoma.
AuthorsWetterskog D, Moshiri A, Ozaki T, Uramoto H, Nakagawara A, Funa K,
JournalMol Cancer Res
PubMed ID19952113
We have previously characterized how p53 family proteins control the transcriptional regulation of the platelet-derived growth factor beta-receptor (PDGFRB) and found that DeltaNp73alpha, acting dominant-negatively to p53 and p73, can upregulate PDGFRB promoter activity. Here, we report that PDGFRB regulation differs between two neuroblastoma cell lines, correlating with the actions ... More
Cloning human herpes virus 6A genome into bacterial artificial chromosomes and study of DNA replication intermediates.
AuthorsBorenstein R, Frenkel N,
JournalProc Natl Acad Sci U S A
PubMed ID19858479
Cloning of large viral genomes into bacterial artificial chromosomes (BACs) facilitates analyses of viral functions and molecular mutagenesis. Previous derivations of viral BACs involved laborious recombinations within infected cells. We describe a single-step production of viral BACs by direct cloning of unit length genomes, derived from circular or head-to-tail concatemeric ... More
Development of an optimized RNA-based murine norovirus reverse genetics system.
AuthorsYunus MA, Chung LM, Chaudhry Y, Bailey D, Goodfellow I,
JournalJ Virol Methods
PubMed ID20637238
Murine norovirus (MNV), identified in 2003, is the only norovirus which replicates efficiently in tissue culture and as a result has been used extensively as a model for human noroviruses, a major cause of acute gastroenteritis. The current report describes the generation of a new approach to reverse genetics recovery ... More
Induction of liver steatosis and lipid droplet formation in ATF6alpha-knockout mice burdened with pharmacological endoplasmic reticulum stress.
AuthorsYamamoto K, Takahara K, Oyadomari S, Okada T, Sato T, Harada A, Mori K,
JournalMol Biol Cell
PubMed ID20631254
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates homeostatic responses collectively termed the unfolded protein response. Among the three principal signaling pathways operating in mammals, activating transcription factor (ATF)6alpha plays a pivotal role in transcriptional induction of ER-localized molecular chaperones and folding enzymes as well as components of ... More
Production of non-fucosylated antibodies by co-expression of heterologous GDP-6-deoxy-D-lyxo-4-hexulose reductase.
Authorsvon Horsten HH, Ogorek C, Blanchard V, Demmler C, Giese C, Winkler K, Kaup M, Berger M, Jordan I, Sandig V,
JournalGlycobiology
PubMed ID20639190
All IgG-type antibodies are N-glycosylated in their Fc part at Asn-297. Typically, a fucose residue is attached to the first N-acetylglucosamine of these complex-type N-glycans. Antibodies lacking core fucosylation show a significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and an increased efficacy of anti-tumor activity. In cases where the clinical efficacy ... More
The M type K15 protein of Kaposi's sarcoma-associated herpesvirus regulates microRNA expression via its SH2-binding motif to induce cell migration and invasion.
AuthorsTsai YH, Wu MF, Wu YH, Chang SJ, Lin SF, Sharp TV, Wang HW,
JournalJ Virol
PubMed ID18971265
Kaposi's sarcoma (KS) associated herpesvirus (KSHV) is the etiological agent of KS. In vivo, KS is a tumor capable of spreading throughout the body, and pulmonary metastasis is observed clinically. In vitro, KSHV induces the invasiveness of endothelial cells. The KSHV open reading frame K15 is a KSHV-specific gene encoding ... More
Suppression of ADAM17-mediated Lyn/Akt pathways induces apoptosis of human leukemia U937 cells: Bungarus multicinctus protease inhibitor-like protein-1 uncovers the cytotoxic mechanism.
AuthorsLiu WH, Chang LS,
JournalJ Biol Chem
PubMed ID20679348
Cell surface proteases have been demonstrated to play an important role in facilitating cell invasion into the extracellular matrix and may contribute significantly to extracellular matrix degradation by metastatic cancer cells. Abundant expression of these enzymes is associated with poor prognosis. Thus, protease inhibitors that repress cell surface proteases may ... More
Glucosamine treatment-mediated O-GlcNAc modification of paxillin depends on adhesion state of rat insulinoma INS-1 cells.
AuthorsKwak TK, Kim H, Jung O, Lee SA, Kang M, Kim HJ, Park JM, Kim SH, Lee JW,
JournalJ Biol Chem
PubMed ID20829364
Protein-protein interactions and/or signaling activities at focal adhesions, where integrin-mediated adhesion to extracellular matrix occurs, are critical for the regulation of adhesion-dependent cellular functions. Although the phosphorylation and activities of focal adhesion molecules have been intensively studied, the effects of the O-GlcNAc modification of their Ser/Thr residues on cellular functions ... More
Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells.
AuthorsEva R, Dassie E, Caswell PT, Dick G, ffrench-Constant C, Norman JC, Fawcett JW,
JournalJ Neurosci
PubMed ID20810886
Integrins play an important part in axon growth, but integrin traffic in neurons is poorly understood. Expression of the tenascin-C-binding integrin alpha9 promotes axon regeneration. We have therefore studied the mechanism by which alpha9 integrin and its partner beta1 are trafficked along axons and at the growth cone using adult ... More
Mouse period 2 mRNA circadian oscillation is modulated by PTB-mediated rhythmic mRNA degradation.
AuthorsWoo KC, Kim TD, Lee KH, Kim DY, Kim W, Lee KY, Kim KT,
JournalNucleic Acids Res
PubMed ID19010962
Circadian mRNA oscillations are the main feature of core clock genes. Among them, period 2 is a key component in negative-feedback regulation, showing robust diurnal oscillations. Moreover, period 2 has been found to have a physiological role in the cell cycle or the tumor suppression. The present study reports that ... More