Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells.
AuthorsVlotides G, Chen YH, Eigler T, Ren SG, Melmed S
JournalEndocrinology
PubMed ID19359387
'To investigate paracrine regulation of pituitary cell growth, we tested fibroblast growth factor (FGF) regulation of TtT/GF folliculostellate (FS) cells. FGF-2, and FGF-4 markedly induced cell proliferation, evidenced by induction of pituitary tumor transforming gene-1 (Pttg1) mRNA expression and percentage of cells in S phase. Signaling for FGF-2-induced FS cell ... More
Deregulation of mitochondrial membrane potential by mitochondrial insertion of granzyme B and direct Hax-1 cleavage.
'The cytoplasm and the nucleus have been identified as activity sites for granzyme B (GrB) following its delivery from cytotoxic lymphocyte granules into target cells. Here we report on the ability of exogenous GrB to insert into and function within a proteinase K-resistant mitochondrial compartment. We identified Hax-1 (HS-1-associated protein ... More
Regulation of cardiac stress signaling by protein kinase d1.
AuthorsHarrison BC, Kim MS, van Rooij E, Plato CF, Papst PJ, Vega RB, McAnally JA, Richardson JA, Bassel-Duby R, Olson EN, McKinsey TA
JournalMol Cell Biol
PubMed ID16648482
'In response to pathological stresses such as hypertension or myocardial infarction, the heart undergoes a remodeling process that is associated with myocyte hypertrophy, myocyte death, and fibrosis. Histone deacetylase 5 (HDAC5) is a transcriptional repressor of cardiac remodeling that is subject to phosphorylation-dependent neutralization in response to stress signaling. Recent ... More
Simultaneous fitting of real-time PCR data with efficiency of amplification modeled as Gaussian function of target fluorescence.
AuthorsBatsch A, Noetel A, Fork C, Urban A, Lazic D, Lucas T, Pietsch J, Lazar A, Schomig E, Grundemann D
JournalBmc Bioinformatics
PubMed ID18267040
'BACKGROUND: In real-time PCR, it is necessary to consider the efficiency of amplification (EA) of amplicons in order to determine initial target levels properly. EAs can be deduced from standard curves, but these involve extra effort and cost and may yield invalid EAs. Alternatively, EA can be extracted from individual ... More
Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.
AuthorsBrocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V
JournalJ Biol Chem
PubMed ID20207735
'Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects ... More
Nuclear respiratory factor 2 induces the expression of many but not all human proteins acting in mitochondrial DNA transcription and replication.
AuthorsBruni F, Polosa PL, Gadaleta MN, Cantatore P, Roberti M
JournalJ Biol Chem
PubMed ID19951946
'In mammals, NRF-2 (nuclear respiratory factor 2), also named GA-binding protein, is an Ets family transcription factor that controls many genes involved in cell cycle progression and protein synthesis as well as in mitochondrial biogenesis. In this paper, we analyzed the role of NRF-2 in the regulation of human ... More
Activation of Nrf2 by cadmium and its role in protection against cadmium-induced apoptosis in rat kidney cells
AuthorsChen, J; Shaikh, ZA
Journal
PubMed ID
'Kidney is the primary target organ in chronic cadmium (Cd) toxicity, and oxidative stress plays an important role in this process. The nuclear transcription factor Nrf2 binds to antioxidant response elements (AREs) and regulates genes involved in protecting cells from oxidative damage. Whether kidney cells respond to Cd by activating ... More
A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB signaling.
AuthorsWu J, Lei G, Mei M, Tang Y, Li H
JournalJ Biol Chem
PubMed ID20228063
'C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-kappaB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of ... More
Combined proteomic-RNAi screen for host factors involved in human hepatitis delta virus replication.
AuthorsCao D, Haussecker D, Huang Y, Kay MA
JournalRna
PubMed ID19776158
'Human hepatitis delta virus (HDV) is the only animal virus known to replicate its RNA genome using a host polymerase because its only virally encoded proteins, the small and large hepatitis delta antigens (HDAg-S and HDAg-L), lack polymerase activity. Although this makes HDV an ideal model system to study RNA-directed ... More
CXCR4 Expression on Activated B Cells Is Downregulated by CD63 and IL-21.
AuthorsYoshida N, Kitayama D, Arima M, Sakamoto A, Inamine A, Watanabe-Takano H, Hatano M, Koike T, Tokuhisa T
JournalJ Immunol
PubMed ID21270405
'CXCR4 expression is critical for localization of centroblasts in the dark zone of germinal centers (GCs), and centrocytes downregulate CXCR4 and thus leave the dark zone to reside in the light zone. However, mechanisms governing CXCR4 downregulation on centrocytes are not known. In this study, we show that the amount ... More
Role of SRC kinases in mobilization of glycosylphosphatidylinositol-anchored decay-accelerating factor by dr fimbria-positive adhering bacteria.
AuthorsQueval CJ, Nicolas V, Beau I
JournalInfect Immun
PubMed ID21518786
'Afa/Dr fimbriae constitute the major virulence factor of diffusely adhering Escherichia coli (Afa/Dr DAEC). After recognizing membrane-bound signaling receptors, they trigger cell responses. One of these receptors is the human decay-accelerating factor (hDAF). It has previously been reported that the binding of Afa/Dr fimbriae to hDAF quickly induces recruitment of ... More
Mitogen stimulation cooperates with telomere shortening to activate DNA damage responses and senescence signaling.
AuthorsSatyanarayana A, Greenberg RA, Schaetzlein S, Buer J, Masutomi K, Hahn WC, Zimmermann S, Martens U, Manns MP, Rudolph KL
JournalMol Cell Biol
PubMed ID15169907
'Replicative senescence is induced by critical telomere shortening and limits the proliferation of primary cells to a finite number of divisions. To characterize the activity status of the replicative senescence program in the context of cell cycle activity, we analyzed the senescence phenotypes and signaling pathways in quiescent ... More
CD28 signaling in T regulatory precursors requires p56lck and rafts integrity to stabilize the Foxp3 message.
AuthorsNazarov-Stoica C, Surls J, Bona C, Casares S, Brumeanu TD
JournalJ Immunol
PubMed ID19109140
'Naturally occurring CD4(+)25(high)Foxp3(+) T regulatory (T-reg) cells are critical for maintaining tolerance to self and non-self Ags. The Foxp3 master-regulatory gene and CD28 costimulation are both required for thymic development and suppressogenic function of CD4(+)25(high)Foxp3(+) T-regs. Herein, we show that the sole CD28 stimulation of T-reg thymic precursors augments Foxp3 ... More
Expression and roles of pannexins in ATP release in the pituitary gland.
AuthorsLi S, Bjelobaba I, Yan Z, Kucka M, Tomic M, Stojilkovic SS
JournalEndocrinology
PubMed ID21467198
'Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show ... More
c-Abl mediates high NaCl-induced phosphorylation and activation of the transcription factor TonEBP/OREBP.
AuthorsGallazzini M, Yu MJ, Gunaratne R, Burg MB, Ferraris JD
JournalFaseb J
PubMed ID20585028
'The transcription factor TonEBP/OREBP promotes cell survival during osmotic stress. High NaCl-induced phosphorylation of TonEBP/OREBP at tyrosine-143 was known to be an important factor in increasing its activity in cell culture. We now find that TonEBP/OREBP also is phosphorylated at tyrosine-143 in rat renal inner medulla, dependent on the interstitial ... More
Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4.
AuthorsKnowles HJ, Cleton-Jansen AM, Korsching E, Athanasou NA
JournalFaseb J
PubMed ID20667978
'Hypoxia and the hypoxia-inducible factor (HIF) transcription factor regulate angiogenic-osteogenic coupling and osteoclast-mediated bone resorption. To determine how HIF might coordinate osteoclast and osteoblast function, we studied angiopoietin-like 4 (ANGPTL4), the top HIF target gene in an Illumina HumanWG-6 v3.0 48k array of normoxic vs. hypoxic osteoclasts differentiated from human ... More
Equilibrative nucleoside transporter 1 plays an essential role in cardioprotection.
AuthorsRose JB, Naydenova Z, Bang A, Eguchi M, Sweeney G, Choi DS, Hammond JR, Coe IR
JournalAm J Physiol Heart Circ Physiol
PubMed ID20035027
'To better understand the role of equilibrative nucleoside transporters (ENT) in purine nucleoside-dependent physiology of the cardiovascular system, we investigated whether the ENT1-null mouse heart was cardioprotected in response to ischemia (coronary occlusion for 30 min followed by reperfusion for 2 h). We observed that ENT1-null mouse hearts showed significantly ... More
The human cathelicidin LL-37 modulates the activities of the P2X7 receptor in a structure-dependent manner.
AuthorsTomasinsig L, Pizzirani C, Skerlavaj B, Pellegatti P, Gulinelli S, Tossi A, Di Virgilio F, Zanetti M
JournalJ Biol Chem
PubMed ID18765670
'Extracellular ATP, released at sites of inflammation or tissue damage, activates the P2X(7) receptor, which in turn triggers a range of responses also including cell proliferation. In this study the ability of the human cathelicidin LL-37 to stimulate fibroblast growth was inhibited by commonly used P2X(7) blockers. We ... More
TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.
AuthorsLim DM, Narasimhan S, Michaylira CZ, Wang ML
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID19779021
'Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. ... More
Molecular mechanism for adiponectin-dependent M2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin.
AuthorsMandal P, Pratt BT, Barnes M, McMullen MR, Nagy LE
JournalJ Biol Chem
PubMed ID21357416
'The anti-inflammatory effects of globular adiponectin (gAcrp) are mediated by IL-10/heme oxygenase 1 (HO-1)-dependent pathways. Although full-length (flAcrp) adiponectin also suppresses LPS-induced pro-inflammatory signaling, its signaling mechanisms are not yet understood. The aim of this study was to examine the differential mechanisms by which gAcrp and flAcrp suppress pro-inflammatory signaling ... More
Activation of LXR increases acyl-CoA synthetase activity through direct regulation of ACSL3 in human placental trophoblast cells.
'Placental fatty acid transport and metabolism are important for proper growth and development of the feto-placental unit. The nuclear receptors, liver X receptors alpha and beta (LXRalpha and LXRbeta), are key regulators of lipid metabolism in many tissues, but little is known about their role in fatty acid ... More
CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock.
AuthorsIsojima Y, Nakajima M, Ukai H, Fujishima H, Yamada RG, Masumoto KH, Kiuchi R, Ishida M, Ukai-Tadenuma M, Minami Y, Kito R, Nakao K, Kishimoto W, Yoo SH, Shimomura K, Takao T, Takano A, Kojima T, Nagai K, Sakaki Y, Takahashi JS, Ueda HR
JournalProc Natl Acad Sci U S A
PubMed ID19805222
'A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze the biochemical processes underlying this flexible-yet-robust characteristic, we examined the effects of 1,260 pharmacologically active compounds in mouse and human clock cell lines. Compounds that markedly (>10 s.d.) lengthened the ... More
Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells.
AuthorsCocco C, Canale S, Frasson C, Di Carlo E, Ognio E, Ribatti D, Prigione I, Basso G, Airoldi I
JournalBlood
PubMed ID20671120
'Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric ... More
Trauma and hemorrhage-induced acute hepatic insulin resistance: dominant role of tumor necrosis factor-alpha.
AuthorsXu J, Kim HT, Ma Y, Zhao L, Zhai L, Kokorina N, Wang P, Messina JL
JournalEndocrinology
PubMed ID18187553
'It has long been known that injury, infections, and other critical illnesses are often associated with hyperglycemia and hyperinsulinemia. Mortality of critically ill patients is greatly reduced by intensive insulin therapy, suggesting the significance of reversing or compensating for the development of acute insulin resistance. However, the development of ... More
Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability.
AuthorsPires IM, Bencokova Z, Milani M, Folkes LK, Li JL, Stratford MR, Harris AL, Hammond EM
JournalCancer Res
PubMed ID20103649
'Questions exist concerning the effects of acute versus chronic hypoxic conditions on DNA replication and genomic stability that may influence tumorigenesis. Severe hypoxia causes replication arrest independent of S-phase checkpoint, DNA damage response, or transformation status. Arrests occur during both the initiation and elongation phases of DNA replication, correlated ... More
Semliki forest virus-induced endoplasmic reticulum stress accelerates apoptotic death of mammalian cells.
AuthorsBarry G, Fragkoudis R, Ferguson MC, Lulla A, Merits A, Kohl A, Fazakerley JK
JournalJ Virol
PubMed ID20427528
'The alphavirus Semliki Forest virus (SFV) and its derived vectors induce apoptosis in mammalian cells. Here, we show that apoptosis is associated with the loss of mitochondrial membrane potential followed by the activation of caspase-3, caspase-8, and caspase-9. Cell death can be partially suppressed by treatment with the pan-caspase inhibitor ... More
Thrombin-cleaved COOH(-) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells.
AuthorsMi Z, Oliver T, Guo H, Gao C, Kuo PC
JournalCancer Res
PubMed ID17483319
'Osteopontin is a glycoprotein that has been linked to metastatic function in breast, lung, and prostate cancers. However, the mechanism by which osteopontin acts to induce metastatic properties is largely unknown. One intriguing feature of osteopontin is the presence of a conserved thrombin cleavage site that is COOH-terminal from a ... More
Repair of nitric oxide-damaged DNA in beta-cells requires JNK-dependent GADD45alpha expression.
AuthorsHughes KJ, Meares GP, Chambers KT, Corbett JA
JournalJ Biol Chem
PubMed ID19648647
'Proinflammatory cytokines induce nitric oxide-dependent DNA damage and ultimately beta-cell death. Not only does nitric oxide cause beta-cell damage, it also activates a functional repair process. In this study, the mechanisms activated by nitric oxide that facilitate the repair of damaged beta-cell DNA are examined. JNK plays a central regulatory ... More
Mechanical stretch-induced RhoA activation is mediated by the RhoGEF Vav2 in mesangial cells
'Increased intraglomerular pressure is an important hemodynamic determinant of glomerulosclerosis, and can be modelled in vitro by exposing mesangial cells (MC) to cyclic mechanical stretch. We have previously shown that the GTPase RhoA mediates stretch-induced fibronectin production. Here we investigate the role of the RhoGEF Vav2 in the activation of ... More
Cardiac myosin is a substrate for zipper-interacting protein kinase (ZIPK).
AuthorsChang AN, Chen G, Gerard RD, Kamm KE, Stull JT
JournalJ Biol Chem
PubMed ID20038585
'Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain (RLC) to promote membrane blebbing. ZIPK mRNA and protein are abundant in heart tissue and isolated ventricular neonatal rat cardiac myocytes. An unbiased ... More
FOXO1A is a target for HER2-overexpressing breast tumors.
AuthorsWu Y, Shang X, Sarkissyan M, Slamon D, Vadgama JV
JournalCancer Res
PubMed ID20551062
'Trastuzumab treatment has improved the overall survival of HER2-overexpressing breast cancer patients. However, many of these patients will eventually become resistant to treatment. The mechanisms that contribute to resistance to trastuzumab are unknown. In this study, we tested the hypothesis that targeting of the FKHR transcription factor FOXO1A in HER2-overexpressing ... More
Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity.
AuthorsNagai S, Takenaka K, Nachagari D, Rose C, Domoney K, Sun D, Sparreboom A, Schuetz JD
JournalCancer Res
PubMed ID21245102
'Purine nucleoside antimetabolites, such as clofarabine, are effective antileukemic agents. However, their effectiveness depends on an initial activation step in which they are monophosphorylated by deoxycytidine kinase (dCK). Some purine nucleoside antimetabolites and their monophosphate derivatives are exported by the ABC transporter ABCG2. Because clofarabine is a dCK substrate, and ... More
Regulation of the embryonic morphogen Nodal by Notch4 facilitates manifestation of the aggressive melanoma phenotype.
AuthorsHardy KM, Kirschmann DA, Seftor EA, Margaryan NV, Postovit LM, Strizzi L, Hendrix MJ
JournalCancer Res
PubMed ID21159651
'Metastatic melanoma is an aggressive skin cancer associated with poor prognosis. The reactivation of the embryonic morphogen Nodal in metastatic melanoma has previously been shown to regulate the aggressive behavior of these tumor cells. During the establishment of left-right asymmetry in early vertebrate development, Nodal expression is specifically regulated by ... More
HDAC4 inhibits cell-cycle progression and protects neurons from cell death
'HDAC4 is a Class II histone deacetylase (HDAC) that is highly expressed in the brain, but whose functional significance in the brain is not known. We show that forced expression of HDAC4 in cerebellar granule neurons protects them against low potassium-induced apoptosis. HDAC4 also protects HT22 neuroblastoma cells from death ... More
NORE1B is a putative tumor suppressor in hepatocarcinogenesis and may act via RASSF1A.
AuthorsMacheiner D, Gauglhofer C, Rodgarkia-Dara C, Grusch M, Brachner A, Bichler C, Kandioler D, Sutterluty H, Mikulits W, Schulte-Hermann R, Grasl-Kraupp B
JournalCancer Res
PubMed ID19118008
'Recently, we found epigenetic silencing of the Ras effector genes NORE1B and/or RASSF1A in 97% of the hepatocellular carcinoma (HCC) investigated. This is strong evidence that the two genes are of major significance in hepatocarcinogenesis. Although RASSF1A serves as a tumor suppressor gene, the functions of NORE1B are largely unknown. ... More
The expression of heparin-binding epidermal growth factor-like growth factor by regulatory macrophages.
AuthorsEdwards JP, Zhang X, Mosser DM
JournalJ Immunol
PubMed ID19201846
'We previously described a population of regulatory macrophages that produced high levels of IL-10 and low levels of IL-12/23. We now describe and characterize the expression of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) by these macrophages. HB-EGF has previously been associated with a number of physiological and ... More
Pro-photoreceptor activity of chick neurogenin1.
AuthorsYan RT, He L, Wang SZ
JournalInvest Ophthalmol Vis Sci
PubMed ID19578021
'PURPOSE: Better understanding of photoreceptor fate specification may lead to efficient production of photoreceptors for cell replacement studies. The authors investigated the role of proneural bHLH gene neurogenin1 (ngn1) in photoreceptor genesis using the chick retina. METHODS: In situ hybridization was used to delineate the spatial and temporal ... More
Direct Membrane Association Drives Mitochondrial Fission by the Parkinson Disease-associated Protein {alpha}-Synuclein.
'The protein alpha-synuclein has a central role in Parkinson disease, but the mechanism by which it contributes to neural degeneration remains unknown. We now show that the expression of alpha-synuclein in mammalian cells, including neurons in vitro and in vivo, causes the fragmentation of mitochondria. The effect is specific for ... More
Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages.
AuthorsSugamura K, Sugiyama S, Nozaki T, Matsuzawa Y, Izumiya Y, Miyata K, Nakayama M, Kaikita K, Obata T, Takeya M, Ogawa H
JournalCirculation
PubMed ID19103987
'"BACKGROUND: Cannabinoid 1 (CB1) receptor blockade with rimonabant represents a clinical therapeutic strategy for obesity. Recently, the role of the endocannabinoid system has been described in peripheral organs. We sought to determine whether the endocannabinoid system could be involved in human atherosclerosis and whether CB1 receptor blockade could modulate proinflammatory ... More
Real-time reverse-transcription loop-mediated isothermal amplification for rapid detection of rift valley Fever virus.
AuthorsPeyrefitte CN, Boubis L, Coudrier D, Bouloy M, Grandadam M, Tolou HJ, Plumet S
JournalJ Clin Microbiol
PubMed ID18799705
'"The development and validation of a one-step, single-tube, real-time accelerated reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the detection of the L RNA segment of Rift Valley fever virus (RVFV) are described. The assay was performed at a constant temperature (63 degrees C), with a real-time follow-up using a LightCycler ... More
Regulation of alternative macrophage activation by galectin-3.
AuthorsMacKinnon AC, Farnworth SL, Hodkinson PS, Henderson NC, Atkinson KM, Leffler H, Nilsson UJ, Haslett C, Forbes SJ, Sethi T
JournalJ Immunol
PubMed ID18250477
'Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative ... More
Antisense artifacts in transcriptome microarray experiments are resolved by actinomycin D.
'Recent transcription profiling studies have revealed an unanticipatedly large proportion of antisense transcription across eukaryotic and bacterial genomes. However, the extent and significance of antisense transcripts is controversial partly because experimental artifacts are suspected. Here, we present a method to generate clean genome-wide transcriptome profiles, using actinomycin D (ActD) during ... 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
Site-specific reverse splicing of a HEG-containing group I intron in ribosomal RNA.
AuthorsBirgisdottir AB, Johansen S
JournalNucleic Acids Res
PubMed ID15817568
'The wide, but scattered distribution of group I introns in nature is a result of two processes; the vertical inheritance of introns with or without losses, and the occasional transfer of introns across species barriers. Reversal of the group I intron self-splicing reaction, termed reverse splicing, coupled with reverse ... More
Role of xanthine oxidase activation and reduced glutathione depletion in rhinovirus induction of inflammation in respiratory epithelial cells.
AuthorsPapi A, Contoli M, Gasparini P, Bristot L, Edwards MR, Chicca M, Leis M, Ciaccia A, Caramori G, Johnston SL, Pinamonti S
JournalJ Biol Chem
PubMed ID18678861
'Rhinoviruses are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. We previously reported rapid rhinovirus induction of intracellular superoxide anion, resulting in NF-kappaB activation and pro-inflammatory molecule production. The mechanisms of rhinovirus superoxide induction are poorly understood. Here we found that ... More
Pro-Photoreceptor Activity of Chick neurogenin1
AuthorsYan, RT; He, L; Wang, SZ
Journal
PubMed ID
'PURPOSE. Better understanding of photoreceptor fate specification may lead to efficient production of photoreceptors for cell replacement studies. The authors investigated the role of proneural bHLH gene neurogenin1 (ngn1) in photoreceptor genesis using the chick retina. METHODS. In situ hybridization was used to delineate the spatial and temporal pattern ... More
Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route.
AuthorsPoirier S, Mayer G, Poupon V, McPherson PS, Desjardins R, Ly K, Asselin MC, Day R, Duclos FJ, Witmer M, Parker R, Prat A, Seidah NG
JournalJ Biol Chem
PubMed ID19635789
'Elevated levels of plasma low density lipoprotein (LDL)-cholesterol, leading to familial hypercholesterolemia, are enhanced by mutations in at least three major genes, the LDL receptor (LDLR), its ligand apolipoprotein B, and the proprotein convertase PCSK9. Single point mutations in PCSK9 are associated with either hyper- or hypocholesterolemia. Accordingly, PCSK9 ... More
Sp1-dependent activation of HDAC7 is required for platelet-derived growth factor-BB-induced smooth muscle cell differentiation from stem cells.
AuthorsZhang L, Jin M, Margariti A, Wang G, Luo Z, Zampetaki A, Zeng L, Ye S, Zhu J, Xiao Q
JournalJ Biol Chem
PubMed ID20889501
'We have previously demonstrated that histone deacetylase 7 (HDAC7) expression and splicing play an important role in smooth muscle cell (SMC) differentiation from embryonic stem (ES) cells, but the molecular mechanisms of increased HDAC7 expression during SMC differentiation are currently unknown. In this study, we found that platelet-derived growth factor-BB ... More
Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
'Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3'' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA ... More
Opposing roles for Akt1 and Akt2 in Rac/Pak signaling and cell migration.
'The Akt/PKB isoforms have different roles in animals, with Akt2 primarily regulating metabolic signaling and Akt1 regulating growth and survival. Here we show distinct roles for Akt1 and Akt2 in mouse embryo fibroblast cell migration and regulation of the cytoskeleton. Akt1-deficient cells responded poorly to platelet-derived growth factor while Akt2-deficient ... More
Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML.
AuthorsHaefliger S, Klebig C, Schaubitzer K, Schardt J, Timchenko N, Mueller BU, Pabst T
JournalBlood
PubMed ID21471526
'Deregulation of the myeloid key transcription factor CEBPA is a common event in acute myeloid leukemia (AML). We previously reported that the chaperone calreticulin is activated in subgroups of AML patients and that calreticulin binds to the stem loop region of the CEBPA mRNA, thereby blocking CEBPA translation. In this ... More
BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death.
AuthorsKuwae A, Matsuzawa T, Ishikawa N, Abe H, Nonaka T, Fukuda H, Imajoh-Ohmi S, Abe A,
JournalJ Biol Chem
PubMed ID16407269
'In Bordetella bronchiseptica, the functional type III secretion system (TTSS) is required for the induction of necrotic cell death in infected mammalian cells. To identify the factor(s) involved in necrotic cell death, type III-secreted proteins from B. bronchiseptica were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization ... More
Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc.
AuthorsCaldon CE, Sergio CM, Schutte J, Boersma MN, Sutherland RL, Carroll JS, Musgrove EA
JournalMol Cell Biol
PubMed ID19564413
'During estrogen-induced proliferation, c-Myc and cyclin D1 initiate independent pathways that activate cyclin E1-Cdk2 by sequestration and/or downregulation of the CDK inhibitor p21(Waf1/Cip1), without significant increases in cyclin E1 protein levels. In contrast, cyclin E2 undergoes a marked increase in expression, which occurs within 9 to 12 h of estrogen ... More
Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats.
AuthorsM Rindler P, Clark RM, Pollard LM, De Biase I, Bidichandani SI
JournalNucleic Acids Res
PubMed ID17142224
"Friedreich ataxia is caused by an expanded (GAA.TTC)n sequence in intron 1 of the FXN gene. Small pool PCR analysis showed that pure (GAA.TTC)44+ sequences at the FXN locus are unstable in somatic cells in vivo, displaying both expansions and contractions. On searching the entire human and mouse genomes ... More
T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinase.
Authorsde Souza AJ, Oak JS, Jordanhazy R, DeKruyff RH, Fruman DA, Kane LP
JournalJ Immunol
PubMed ID18453570
Ligation of the transmembrane protein T cell Ig and mucin domain (Tim)-1 can costimulate T cell activation. Agonistic Abs to Tim-1 are also capable of inducing T cell activation without additional stimuli. However, little is known about the biochemical mechanisms underlying T cell stimulation or costimulation through Tim-1. We show ... More
The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease.
AuthorsPacker AN, Xing Y, Harper SQ, Jones L, Davidson BL
JournalJ Neurosci
PubMed ID19118166
The transcription factor REST silences neuronal gene expression in non-neuronal cells. In neurons, the protein is sequestered in the cytoplasm in part through binding to huntingtin. Polyglutamine expansions in huntingtin, which causes Huntington's disease (HD), abrogates REST-huntingtin binding. Consequently, REST translocates to the nucleus, occupies RE1 repressor sequences and ... More
Cutting edge: IL-4 induces suppressor of cytokine signaling-3 expression in B cells by a mechanism dependent on activation of p38 MAPK.
AuthorsCanfield S, Lee Y, Schroder A, Rothman P
JournalJ Immunol
PubMed ID15728454
The signaling cascade initiated by IL-4 is classically divisible into two major pathways: one mediated by STAT6, and the other by insulin receptor substrates-1 and -2 via activation of PI3K. In murine splenic B cells, the suppressor of cytokine signaling (SOCS)3 is inducible by IL-4 via a mechanism independent of ... More
Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6.
AuthorsYanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S
JournalJ Biol Chem
PubMed ID19386608
p2y5 is an orphan G protein-coupled receptor that is closely related to the fourth lysophosphatidic acid (LPA) receptor, LPA4. Here we report that p2y5 is a novel LPA receptor coupling to the G13-Rho signaling pathway. ""LPA receptor-null"""" RH7777 and B103 cells exogenously expressing p2y5 showed [3H]LPA binding, LPA-induced [35S]guanosine ... More
NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals.
AuthorsAbolhassani N, Iyama T, Tsuchimoto D, Sakumi K, Ohno M, Behmanesh M, Nakabeppu Y,
JournalNucleic Acids Res
PubMed ID20081199
Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa(-) mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa(-) embryos than in wild-type embryos. Therefore, we examined the effects ... More
The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation.
AuthorsFernandez-Sanchez ME, Sechet E, Margottin-Goguet F, Rogge L, Bianchi E
JournalJ Biol Chem
PubMed ID20378537
The COP9 signalosome (CSN) is an essential multisubunit complex that regulates the activity of cullin-RING ubiquitin ligases by removing the ubiquitin-like peptide NEDD8 from cullins. Here, we demonstrate that the CSN can affect other components of the ubiquitination cascade. Down-regulation of human CSN4 or CSN5 induced proteasome-mediated degradation of the ... More
Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries
Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons is an essential step in NMDAR-mediated excitotoxic ... More
V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway.
AuthorsHurtado-Lorenzo A, Skinner M, El Annan J, Futai M, Sun-Wada GH, Bourgoin S, Casanova J, Wildeman A, Bechoua S, Ausiello DA, Brown D, Marshansky V
JournalNat Cell Biol
PubMed ID16415858
The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. ... More
Mammalian pre-mRNA 3′ End Processing Factor CF I(m)68 Functions in mRNA Export
Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA ... More
Btk expression is controlled by Oct and BOB.1/OBF.1.
AuthorsBrunner C, Wirth T
JournalNucleic Acids Res
PubMed ID16582106
BOB.1/OBF.1 is a lymphocyte-restricted transcriptional coactivator. It binds together with the Oct1 and Oct2 transcription factors to DNA and enhances their transactivation potential. Mice deficient for the transcriptional coactivator BOB.1/OBF.1 show several defects in differentiation, function and signaling of B cells. In search of BOB.1/OBF.1 regulated genes we identified ... More
Identification of protein kinases that control ovarian hormone release by selective siRNAs.
AuthorsSirotkin AV, Ovcharenko D, Mlyncek M
JournalJ Mol Endocrinol
PubMed ID19713423
The goal of this study was to identify protein kinases (PKs) that control the secretory activity of human ovarian cells. Cultured ovarian granulosa cells were transfected with 264 siRNA constructs that selectively block the expression of 88 known PKs. The efficiency of transfection and of silencing marker molecules (glyceraldehyde ... More
Interaction of developmental transcription factor HOXC11 with steroid receptor coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer [corrected].
AuthorsMcIlroy M, McCartan D, Early S, O Gaora P, Pennington S, Hill AD, Young LS
JournalCancer Res
PubMed ID20145129
Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used a mass spectrometry-based screen to identify proteins that are associated with the endocrine-resistant phenotype. In this study, we report the identification of a novel pathway of resistance to endocrine ... More
HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1.
AuthorsQuintela-Fandino M, Arpaia E, Brenner D, Goh T, Yeung FA, Blaser H, Alexandrova R, Lind EF, Tusche MW, Wakeham A, Ohashi PS, Mak TW
JournalProc Natl Acad Sci U S A
PubMed ID20133759
Metastasis leads to the death of most cancer patients, and basal breast cancer is the most aggressive breast tumor type. Metastasis involves a complex cell migration process dependent on cytoskeletal remodeling such that targeting such remodeling in tumor cells could be clinically beneficial. Here we show that Hormonally Up-regulated Neu-associated ... More
Fusion of microglia with pyramidal neurons after retroviral infection.
The neurogenic potential of the postnatal neocortex has not been tested previously with a combination of both retroviral and bromodeoxyuridine (BrdU) labeling. Here we report that injections of enhanced green fluorescent protein (eGFP) retrovirus into 134 postnatal rats resulted in GFP labeling of 642 pyramidal neurons in neocortex. GFP-labeled neocortical ... More
Gene knockdown studies revealed CCDC50 as a candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia
AuthorsFarfsing, A; Engel, F; Seiffert, M; Hartmann, E; Ott, G; Rosenwald, A; Stilgenbauer, S; Doehner, H; Boutros, M; Lichter, P; Pscherer, A
Journal
PubMed ID
The two B-cell non-Hodgkin's lymphoma entities, chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), show recurrent chromosomal gains of 3q25-q29, 12q13-q14 and 18q21-q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell ... More
Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1.
AuthorsWells J, Lee B, Cai AQ, Karapetyan A, Lee WJ, Rugg E, Sinha S, Nie Q, Dai X
JournalJ Biol Chem
PubMed ID19700410
Ovol2 belongs to the Ovo family of evolutionarily conserved zinc finger transcription factors that act downstream of key developmental signaling pathways including Wg/Wnt and BMP/TGF-beta. We previously reported Ovol2 expression in the basal layer of epidermis, where epidermal stem/progenitor cells reside. In this work, we use HaCaT human keratinocytes to ... More
Selenoprotein W Modulates Control of Cell Cycle Entry
AuthorsHawkes, WC; Wang, TTY; Alkan, Z; Richter, BD; Dawson, K
Journal
PubMed ID
The present study was conducted to identify targets of selenium (Se) provided to cultured human cells in physiologically relevant doses and forms. Breast and prostate epithelial cells were supplemented with Se provided as 100 nM sodium selenite or high-Se serum and gene expression was profiled with DNA microarrays. Pure sodium ... More
Identification of a mechanochemical checkpoint and negative feedback loop regulating branching morphogenesis
AuthorsDaley, WP; Gulfo, KM; Sequeira, SJ; Larsen, M
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PubMed ID
Cleft formation is the initial step in submandibular salivary gland (SMG) branching morphogenesis, and may result from localized actomyosin-mediated cellular contraction. Since ROCK regulates cytoskeletal contraction, we investigated the effects of ROCK inhibition on mouse SMG ex vivo organ cultures. Pharmacological inhibitors of ROCK, isoform-specific ROCK I but not ROCK ... More
Microtubule disruption targets HIF-1alpha mRNA to cytoplasmic P-bodies for translational repression.
AuthorsCarbonaro M, O'Brate A, Giannakakou P
JournalJ Cell Biol
PubMed ID21220510
The hypoxia inducible factor 1alpha (HIF-1alpha) is overexpressed in solid tumors, driving tumor angiogenesis and survival. However, the mechanisms regulating HIF-1alpha expression in solid tumors are not fully understood. In this study, we find that microtubule integrity and dynamics are intricately involved in orchestrating HIF-1alpha translation. HIF-1alpha messenger RNA (mRNA) ... More
Making sense of antisense: seemingly noncoding RNAs antisense to the master regulator of Kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mRNAs encoding small peptides.
AuthorsXu Y, Ganem D
JournalJ Virol
PubMed ID20357088
The mammalian transcriptome is studded with putative noncoding RNAs, many of which are antisense to known open reading frames (ORFs). Roles in the regulation of their complementary mRNAs are often imputed to these antisense transcripts, but few have been experimentally examined, and such functions remain largely conjectural. Kaposi's sarcoma-associated ... More
Differential effects of anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2, and Bcl-xL on Celecoxib-induced apoptosis
AuthorsRudner, J; Elsaesser, SJ; Mueller, AC; Belka, C; Jendrossek, V
Journal
PubMed ID
The cyclooxygenase-2 inhibitor Celecoxib is a potent inducer of apoptosis in tumor cells. In most cellular systems Celecoxib induces apoptosis via an intrinsic, mitochondrial apoptosis pathway. We recently showed that in Bax-negative Jurkat cells expression of pro-apoptotic Bak is essential for Celecoxib-induced mitochondrial damage and apoptosis induction. Aim of the ... More
Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses.
We provide evidence for the existence of an IFN-regulated cellular pathway involving the mitogen-activated protein kinase (MAPK)-integrating kinase (Mnk) 1. Our data demonstrate that type I (alpha, beta) IFNs induce phosphorylation/activation of Mnk1, which, in turn, regulates phosphorylation of the eukaryotic initiation factor 4E (eIF4E) on Ser-209. Such Mnk ... More
Role of Schlafen 2 (SLFN2) in the generation of interferon alpha-induced growth inhibitory responses.
AuthorsKatsoulidis E, Carayol N, Woodard J, Konieczna I, Majchrzak-Kita B, Jordan A, Sassano A, Eklund EA, Fish EN, Platanias LC
JournalJ Biol Chem
PubMed ID19592487
The precise STAT-regulated gene targets that inhibit cell growth and generate the antitumor effects of Type I interferons (IFNs) remain unknown. We provide evidence that Type I IFNs regulate expression of Schlafens (SLFNs), a group of genes involved in the control of cell cycle progression and growth inhibitory responses. Using ... More
Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesis.
Stimulated inflammatory cells synthesize platelet-activating factor (PAF), but lysates of these cells show little enhancement in PAF synthase activity. We show that human neutrophils contain intracellular plasma PAF acetylhydrolase (PLA2G7), an enzyme normally secreted by monocytes. The esterase inhibitors methyl arachidonoylfluorophosphonate (MAFP), its linoleoyl homolog, and Pefabloc inhibit plasma ... More
p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils.
AuthorsMartyn KD, Kim MJ, Quinn MT, Dinauer MC, Knaus UG
JournalBlood
PubMed ID16099876
The phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays an instrumental role in host defense and contributes to microbicial killing by releasing highly reactive oxygen species. This multicomponent enzyme is composed of membrane and cytosolic components that assemble in the plasma membrane or phagolysosome. While the guanosine S'-triphosphatase (GTPase) ... More
Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum.
AuthorsMcHugh BJ, Buttery R, Lad Y, Banks S, Haslett C, Sethi T
JournalJ Cell Sci
PubMed ID20016066
The integrin family of heterodimeric cell-surface receptors are fundamental in cell-cell and cell-matrix adhesion. Changes to either integrin-ligand affinity or integrin gene expression are central to a variety of disease processes, including inflammation, cardiovascular disease and cancer. In screening for novel activators of integrin-ligand affinity we identified the previously uncharacterised ... More
Overexpression of Prdx6 and resistance to peroxide-induced death in Hepa1-6 cells: Prdx suppression increases apoptosis
Peroxiredoxins are thiol-specific antioxidants that catalyze the reduction of cellular peroxides and protect cells from ROS-mediated damage and death. Peroxiredoxin gene expression is up-regulated in a number of cancers, suggesting a possible role in cancer cell maintenance. Prdx6, a cytoplasmic protein elevated in certain cancers, is highly expressed in liver ... More
Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells.
AuthorsKlunker S, Chong MM, Mantel PY, Palomares O, Bassin C, Ziegler M, Ruckert B, Meiler F, Akdis M, Littman DR, Akdis CA
JournalJ Exp Med
PubMed ID19917773
Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-beta (TGF-beta) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4(+) T cells. This induction seems to be ... More
Cingulin regulates claudin-2 expression and cell proliferation through the small GTPase RhoA.
AuthorsGuillemot L, Citi S
JournalMol Biol Cell
PubMed ID16723500
In mouse embryoid bodies, mutation of the tight junction protein cingulin results in changes in gene expression. Here, we studied the function of cingulin using a gene silencing approach in Madin-Darby canine kidney (MDCK) cells. Cingulin-depleted cells show higher protein and mRNA levels of claudin-2 and ZO-3, increased RhoA ... More
Nuclear degradation of Wilms tumor 1-associating protein and survivin splice variant switching underlie IGF-1-mediated survival.
AuthorsSmall TW, Pickering JG
JournalJ Biol Chem
PubMed ID19605357
WTAP (Wilms tumor 1-associating protein) is a recently identified nuclear protein that is essential for mouse embryo development. The Drosophila homolog of WTAP, Fl(2)d, regulates pre-mRNA splicing; however, the role of WTAP in mammalian cells is uncertain. To elucidate a context for WTAP action, we screened growth and survival factors ... More
The gammaTuRC revisited: a comparative analysis of interphase and mitotic human gammaTuRC redefines the set of core components and identifies the novel subunit GCP8.
AuthorsTeixido-Travesa N, Villen J, Lacasa C, Bertran MT, Archinti M, Gygi SP, Caelles C, Roig J, Luders J
JournalMol Biol Cell
PubMed ID20861304
The gamma-tubulin complex is a multi-subunit protein complex that nucleates microtubule polymerization. gamma-Tubulin complexes are present in all eukaryotes, but size and subunit composition vary. In Drosophila, Xenopus, and humans large gamma-tubulin ring complexes (gammaTuRCs) have been described, which have a characteristic open ring-shaped structure and are composed of a ... More
Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse.
AuthorsGlidewell-Kenney C, Weiss J, Hurley LA, Levine JE, Jameson JL
JournalEndocrinology
PubMed ID18467444
Estrogen, acting via estrogen receptor (ER)alpha, regulates serum gonadotropin levels and pituitary gonadotropin subunit expression. However, the cellular pathways mediating this regulation are unknown. ERalpha signals through classical estrogen response element (ERE)-dependent genomic as well as nonclassical ERE-independent genomic and nongenomic pathways. Using targeted mutagenesis in mice to disrupt ERalpha ... More
Force-induced Myofibroblast Differentiation through Collagen Receptors Is Dependent on Mammalian Diaphanous (mDia).
AuthorsChan MW, Chaudary F, Lee W, Copeland JW, McCulloch CA
JournalJ Biol Chem
PubMed ID20071339
The development of fibrosis promotes the differentiation of myofibroblasts, pro-fibrotic cells, which contribute to tissue dysfunction. Myofibroblast differentiation is dependent on actin assembly, which in response to force, is mediated by various actin-binding proteins including the mammalian Diaphanous-related formins (mDia). We examined the role of mDia in the mechano-sensing pathway ... More
Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.
AuthorsMatsushita K, Morello F, Wu Y, Zhang L, Iwanaga S, Pratt RE, Dzau VJ
JournalJ Biol Chem
PubMed ID20118482
Renin is a key enzyme for cardiovascular and renal homeostasis and is produced by highly specialized endocrine cells in the kidney, known as juxtaglomerular (JG) cells. The nature and origin of these cells remain as mysteries. Previously, we have shown that the nuclear hormone receptor liver X receptor-alpha (LXRalpha) is ... More
Histone deacetylases in fungi: novel members, new facts.
AuthorsTrojer P, Brandtner EM, Brosch G, Loidl P, Galehr J, Linzmaier R, Haas H, Mair K, Tribus M, Graessle S
JournalNucleic Acids Res
PubMed ID12853613
Acetylation is the most prominent modification on core histones that strongly affects nuclear processes such as DNA replication, DNA repair and transcription. Enzymes responsible for the dynamic equilibrium of histone acetylation are histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this paper we describe the identification of novel HDACs ... More
Distinct roles for isoforms of the catalytic subunit of class-IA PI3K in the regulation of behaviour of murine embryonic stem cells.
AuthorsKingham E, Welham M
JournalJ Cell Sci
PubMed ID19509054
Self-renewal of embryonic stem cells (ESCs) is essential for maintenance of pluripotency, which is defined as the ability to differentiate into any specialised cell type comprising the adult organism. Understanding the mechanisms that regulate ESC self-renewal and proliferation is required before ESCs can fulfil their potential in regenerative therapies, and ... More
Knockdown of L calcium channel subtypes: differential effects in neuropathic pain.
AuthorsFossat P, Dobremez E, Bouali-Benazzouz R, Favereaux A, Bertrand SS, Kilk K, Leger C, Cazalets JR, Langel U, Landry M, Nagy F
JournalJ Neurosci
PubMed ID20089916
The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through neuronal L-type voltage-gated calcium channels (LTCs) plays a pivotal role in excitation-transcription coupling, but the involvement of LTCs in chronic pain remains unclear. We used a peptide nucleic ... More
The solute carrier 44A1 is a mitochondrial protein and mediates choline transport.
AuthorsMichel V, Bakovic M
JournalFaseb J
PubMed ID19357133
Choline oxidation to betaine takes place in the mitochondria; however, a protein regulating mitochondrial choline transport was never identified. The purpose of this study was to analyze subcellular localization of the solute carrier 44A1 (SLC44A1), a plasma membrane choline transporter sensitive to inhibition by hemicholinium-3. We generated N- and ... More
Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARalpha and PML-RARalpha.
AuthorsGianni' M, Boldetti A, Guarnaccia V, Rambaldi A, Parrella E, Raska I Jr, Rochette-Egly C, Del Sal G, Rustighi A, Terao M, Garattini E
JournalCancer Res
PubMed ID19155306
The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic ... More
Phospholipase C{beta}1b associates with a Shank3 complex at the cardiac sarcolemma.
AuthorsGrubb DR, Iliades P, Cooley N, Yu YL, Luo J, Filtz TM, Woodcock EA
JournalFaseb J
PubMed ID21148417
Activation of the heterotrimeric G protein Gq causes cardiomyocyte hypertrophy in vivo and in cell models. Our previous studies have shown that responses to activated Gq in cardiomyocytes are mediated exclusively by phospholipase Cbeta1b (PLCbeta1b), because only this PLCbeta subtype localizes at the cardiac sarcolemma. In the current study, we ... More
AML1 enhances the expression of leukotriene B4 type-1 receptor in leukocytes.
AuthorsHashidate T, Murakami N, Nakagawa M, Ichikawa M, Kurokawa M, Shimizu T, Nakamura M
JournalFaseb J
PubMed ID20395453
Leukotriene B4 type-1 receptor (BLT1), which plays a role in various inflammatory diseases, is exclusively expressed in peripheral leukocytes, which suggests that its expression is stringently regulated. However, the precise mechanism of BLT1 expression is not fully understood. Here we report that acute myeloid leukemia 1 (AML1/Runx1) is ... More
Eps15 interacts with ubiquitinated CA3 and mediates its internalization
AuthorsGirao, H; Catarino, S; Pereira, P
Journal
PubMed ID
Gap junctions (GJ) are specialized cell-cell contacts that provide direct intercellular communication (IC) between eukaryotic cells. Regulation of GJIC by degradation of Cx43 has been a matter of debate over the last two decades and both the proteasome and the lysosome have been implicated. However, the underlying mechanism and molecular ... More
Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation.
AuthorsSchmelter M, Ateghang B, Helmig S, Wartenberg M, Sauer H
JournalFaseb J
PubMed ID16636108
Growing stem cells are subjected to mechanical forces, which may initiate differentiation programs. Mechanical strain stimulated cardiovascular differentiation of mouse embryonic stem (ES) cells as evaluated by quantification of contracting cardiac foci and capillary areas, respectively. Mechanical strain rapidly elevated intracellular reactive oxygen species (ROS). After 24 h up-regulation ... More
Focal adhesion kinase is a blood-testis barrier regulator.
AuthorsSiu ER, Wong EW, Mruk DD, Porto CS, Cheng CY
JournalProc Natl Acad Sci U S A
PubMed ID19470647
In mammalian testes, such as rats, the mechanism(s) that regulate blood-testis barrier (BTB) restructuring at stages VIII-IX of the seminiferous epithelial cycle of spermatogenesis to facilitate the transit of preleptotene/leptotene spermatocytes is not known. This is due to the lack of information on the regulatory proteins at the BTB. Herein, ... More
Human copper transporter hCTR1 mediates basolateral uptake of copper into enterocytes: implications for copper homeostasis.
AuthorsZimnicka AM, Maryon EB, Kaplan JH
JournalJ Biol Chem
PubMed ID17627945
Copper is essential for human growth and survival. Enterocytes mediate the absorption of dietary copper from the intestinal lumen into blood as well as utilizing copper for their biosynthetic needs. Currently, the pathways for copper entry into enterocytes remain poorly understood. We demonstrate that the basolateral copper uptake into intestinal ... More
Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the alzheimer amyloid precursor protein.
AuthorsVenkataramani V, Rossner C, Iffland L, Schweyer S, Tamboli IY, Walter J, Wirths O, Bayer TA
JournalJ Biol Chem
PubMed ID20145244
The beta-amyloid precursor protein (APP) represents a type I transmembrane glycoprotein that is ubiquitously expressed. In the brain, it is a key player in the molecular pathogenesis of Alzheimer disease. Its physiological function is however less well understood. Previous studies showed that APP is up-regulated in prostate, colon, pancreatic ... More