Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
interactions between e2f1 and sirt1 regulate apoptotic response to dna damage.the nicotinamide adenine dinucleotide (nad)-dependent deacetylase sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. the mammalian homologue of sir2 (sirt1) regulates p53, nf-kappab and forkhead transcription factors, and is implicated in stress response. this report shows that the cell-cycle and apoptosis regulator e2f1 induces sirt1 expression at the transcriptional level. furthermore, sirt1 binds to e2f1 and inhi ...200616892051
molecular dissection of the munc18c/syntaxin4 interaction: implications for regulation of membrane trafficking.sec1p/munc18 (sm) proteins are believed to play an integral role in vesicle transport through their interaction with snares. different sm proteins have been shown to interact with snares via different mechanisms, leading to the conclusion that their function has diverged. to further explore this notion, in this study, we have examined the molecular interactions between munc18c and its cognate snares as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma m ...200616899085
genome comparison using gene ontology (go) with statistical testing.automated comparison of complete sets of genes encoded in two genomes can provide insight on the genetic basis of differences in biological traits between species. gene ontology (go) is used as a common vocabulary to annotate genes for comparison. current approaches calculate the fold of unweighted or weighted differences between two species at the high-level go functional categories. however, to ensure the reliability of the differences detected, it is important to evaluate their statistical si ...200616901353
a novel krüppel related factor consisting of only a krab domain is expressed in the murine trigeminal ganglion.the largest family of zinc-finger (znf) transcription factors is that containing the krüppel-associated box, or krab domain. the amino-terminal krab domain of these proteins functions as a transcriptional repressor with the downstream znf motifs providing dna-binding specificity. here we report the identification and characterization of a novel murine krüppel-related factor (klf), mif1, which contains a krab domain but lacks a znf motif. western blot analysis identified mif1-like proteins in the ...200616904636
caspase-mediated changes in sir2alpha during apoptosis.silent information regulator 2 (sir2) is an nad(+)-dependent histone deacetylase that establishes repressive chromatin status and extends the life span of both budding yeast and the nematode worm caenorhabditis elegans. there is growing evidence that its mammalian homologue sir2alpha protects cells from stress-induced apoptosis. we report here that mammalian sir2alpha was directly cleaved by both initiator and executioner caspases, and relocated from the nucleus to the cytoplasm in apoptotic cel ...200617027980
[methods for monitoring macroautophagy]. 200616922435
biochemical and genetic analysis of methylenetetrahydrofolate reductase in leishmania metabolism and virulence.methylenetetrahydrofolate reductase (mthfr; ec 1.5.1.20) is the sole enzyme responsible for generation of 5-methyltetrahydrofolate, which is required for methionine synthesis and provision of methyl groups via s-adenosylmethionine. genome analysis showed that leishmania species, unlike trypanosoma brucei and trypanosoma cruzi, contain genes encoding mthfr and two distinct methionine synthases. leishmania mthfr differed from those in other eukaryotes by the absence of a c-terminal regulatory doma ...200617032644
progressive loss of sirt1 with cell cycle withdrawal.sir2 is an nad+-dependent deacetylase that regulates lifespan in yeast, worms and flies. the mammalian orthologs of sir2 include sirt1 in humans and mice. in this study, we analyzed the level of sirt1 in human lung fibroblasts (imr90) and mouse embryonic fibroblasts (mefs) from mice with normal, accelerated, and delayed aging. sirt1 protein, but not mrna, decreased significantly with serial cell passage in both human and murine cells. mouse sirt1 decreased rapidly in prematurely senescent (p44 t ...200616939484
cch1 mediates calcium entry in cryptococcus neoformans and is essential in low-calcium environments.the ability of cryptococcus neoformans to grow at the mammalian body temperature (37 degrees c to 39 degrees c) is a well-established virulence factor. growth of c. neoformans at this physiological temperature requires calcineurin, a ca(2+)/calmodulin-dependent protein phosphatase. when cytosolic calcium concentrations are low ( approximately 50 to 100 nm), calcineurin is inactive and becomes active only when cytosolic calcium concentrations rise ( approximately 1 to 10 microm) through the activ ...200616950930
dna binding and transactivation properties of the schistosoma mansoni constitutive androstane receptor homologue.smcar (schistosoma mansoni constitutive androstane receptor) is a schistosome homologue of the car/pxr/vdr group of nuclear receptors. the p box sequence in the dna binding domain (dbd) of smcar, which is essential in determining the dna binding specificity of nuclear receptors, is different from its vertebrate homologues. previous data demonstrates that smcar binds to a hormone response element containing a single half site agtgca as a monomer. smrxr1 and smrxr2 are two s. mansoni homologues of ...200616962182
resveratrol--a boon for treating alzheimer's disease?resveratrol, a red wine polyphenol, is known to protect against cardiovascular diseases and cancers, as well as to promote antiaging effects in numerous organisms. it also modulates pathomechanisms of debilitating neurological disorders, such as strokes, ischemia, and huntington's disease. the role of resveratrol in alzheimer's disease is still unclear, although some recent studies on red wine bioactive compounds suggest that resveratrol modulates multiple mechanisms of alzheimer's disease patho ...200616766037
peroxisomal fatty acid beta-oxidation is not essential for virulence of candida albicans.phagocytic cells form the first line of defense against infections by the human fungal pathogen candida albicans. recent in vitro gene expression data suggest that upon phagocytosis by macrophages, c. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid beta-oxidation pathway. here, we asked whether fatty acid beta-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by construc ...200616963628
functional interaction of creb binding protein (cbp) with nuclear transport proteins and modulation by hdac inhibitors.nuclear transport proteins such as cse1, nup93 and importin-alpha have recently been shown to be chromatin-associated proteins in yeast, which have unexpected functions in gene regulation. here we report interactions between the mammalian histone acetyltransferase cbp with nuclear transport proteins cas (a cse1 homologue) and importin-alpha (impalpha) and nup93. cas was found to bind the src1 interaction domain (sid) of cbp via a leucine-rich motif in the n-terminus of the protein, that is conse ...200616969114
disruption of protein-protein interaction in the mgl-1 oncoprotein.mammalian homologues of the lethal giant larvae (lgl) tumor suppressor gene have been identified and these homologues can complement the yeast double mutant of sop1 and sop2, the yeast homologue of lgl, as reported previously. in the absence of these genes in yeast, cellular viability is affected at restrictive temperature and salt environments. members of this family contain five or more of the wd-40 repeat motifs, which is known to be involved in protein-protein interaction. in order to invest ...200616969496
identification of tctex2beta, a novel dynein light chain family member that interacts with different transforming growth factor-beta receptors.endoglin is a membrane-inserted protein that is preferentially synthesized in angiogenic vascular endothelial and smooth muscle cells. endoglin associates with members of the transforming growth factor-beta (tgf-beta) receptor family and has been identified as the gene involved in hereditary hemorrhagic telangiectasia. although endoglin is known to affect cell responses to tgf-beta, its mode of action is largely unknown. we performed yeast two-hybrid screening of a human placental cdna library a ...200616982625
ubiquitin-binding motifs in rev1 protein are required for its role in the tolerance of dna damage.rev1 protein is a eukaryotic member of the y family of dna polymerases involved in the tolerance of dna damage by replicative bypass. the precise role(s) of rev1 in this process is not known. here we show, by using the yeast two-hybrid assay and the glutathione s-transferase pull-down assay, that mouse rev1 can physically interact with ubiquitin. the association of rev1 with ubiquitin requires the ubiquitin-binding motifs (ubms) located at the c terminus of rev1. the ubms also mediate the enhanc ...200616982685
the wilms tumour suppressor protein wt1 (+kts isoform) binds alpha-actinin 1 mrna via its zinc-finger domain.mutations in wt1 are associated with developmental syndromes that affect the urogenital system and neoplasms, including wilms tumour, acute myeloid leukemia, and breast and prostate cancers. the wt1 protein belongs to the early growth response family of zinc-finger transcription factors. uniquely to wt1, an evolutionarily conserved alternative splice event inserts the tripeptide kts, between zinc fingers 3 and 4. whereas -kts isoforms bind dna and activate or repress transcription, +kts isoforms ...200617167543
use of the porcine intestinal epithelium (pie)-assay to analyze early stages of colonization by the human fungal pathogen candida albicans.virulence of c. albicans strains can be tested using a mouse model of haematogenously disseminated candida cells. initial steps of host-pathogen contact such as adhesion and colonization are not taken into account due to the injection of candida cells into the blood stream. here we describe an assay, based on the ex vivo usage of porcine intestinal epithelium (pie), that is useful to monitor the early stages of a c. albicans infection. the ability of c. albicans to undergo morphogenetic switchin ...200617139615
expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes.loss of heterozygosity (loh) contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. loh would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because loh would change a cell's phenotype from dichromatic to monochromatic. in addition, loh caused by ...200617042952
alpha-synuclein, oxidative stress and apoptosis from the perspective of a yeast model of parkinson's disease.the neuronal protein alpha-synuclein (alpha-syn) has been suggested to be one of the factors linked to parkinson's disease (pd). several organisms, including the rat, mouse, worm, and fruit fly, are being used to study alpha-syn pathobiology. a new model organism was recently added to this armamentarium: the budding yeast saccharomyces cerevisiae. the yeast system recapitulates many of the findings made with higher eukaryotes. for example, yeast cells expressing alpha-syn accumulate lipid drople ...200617156009
the cytidine deaminases aid and apobec-1 exhibit distinct functional properties in a novel yeast selectable system.activation-induced cytidine deaminase (aid) is indispensable for immunoglobulin maturation by somatic hypermutations and class switch recombination and is supposed to deaminate cytidines in dna, while its homolog apobec-1 edits apolipoprotein (apo) b mrna by cytidine deamination. we studied the editing activity of apobec-1 and aid in yeast using the selectable marker gal4 linked to its specific inhibitor protein gal80 via an apo b cassette (gal4-c) or via the variable region of a mouse immunoglo ...200615963568
characterization of ammonia transport by the kidney rh glycoproteins rhbg and rhcg.the erythrocyte rh-associated glycoprotein (rhag) was recently found to mediate transport of ammonia/ammonium when expressed in xenopus laevis oocytes and yeast saccharomyces cerevisiae. nonerythroid homologs, rhbg and rhcg, are expressed in the mammalian kidney connecting segment and the collecting duct, major sites of urinary ammonia secretion. this study characterizes the transport properties of murine rhbg and rhcg by ammonium analog [14c]methylamine (ma) uptake and two-electrode voltage cla ...200616131648
controlled gene activation and inactivation in the mouse.the emergence of techniques that allow fine manipulation of gene expression in the mouse have changed the way biomedically relevant processes are studied, as they allow their analysis in the living animal. in addition, this has opened the possibility to generate animal models for several human diseases, which are useful both for understanding the disease' s physiopathological mechanisms and for the eventual evaluation of novel therapeutic approaches. many of the gene manipulation systems current ...200616146733
striatal neuronal apoptosis is preferentially enhanced by nmda receptor activation in yac transgenic mouse model of huntington disease.huntington disease (hd), caused by expansion >35 of a polyglutamine tract in huntingtin, results in degeneration of striatal medium spiny neurons (msns). previous studies demonstrated mitochondrial dysfunction, altered intracellular calcium release, and enhanced nmdar-mediated current and apoptosis in cellular and mouse models of hd. here, we exposed cultured msns from yac transgenic mice, expressing full-length human huntingtin with 18, 72, or 128 repeats, to a variety of apoptosis-inducing com ...200616165367
beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury.myelotoxic injury in the bone marrow (bm) as a consequence of total body irradiation (tbi) or granulocyte colony-stimulating factor (g-csf) mobilization results in the deposition of ic3b on bm stroma (stroma-ic3b). in the present study, we have examined how stroma-ic3b interacts with hematopoietic progenitor cells (hpcs) and the role of complement (c) and complement receptor 3 (cr3) in bm injury/repair. we demonstrate here that stroma-ic3b tethers hpcs via the inserted (i) domain of hpc compleme ...200616179370
isolation and characterization of a transcriptional cofactor and its novel isoform that bind the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-gamma.using the dna-binding domain (dbd) and hinge region of human peroxisome proliferator-activated receptor (ppar)-gamma as bait in yeast two-hybrid screen, we isolated partial cdna identical with that of the c terminal of kiaa1769. kiaa1769 encodes a 2080-amino acid protein (molecular mass, 231 kda) that was recently identified to interact with pparalpha and termed pparalpha-interacting cofactor 285 (here referred to as ppargamma-dbd-interacting protein 1 (pdip1)-alpha). pdip1 mrna was expressed in ...200616239304
a computational screen for mammalian pseudouridylation guide h/aca rnas.the box h/aca rna gene family is one of the largest non-protein-coding gene families in eukaryotes and archaea. recently, we developed snogps, a computational screening program for h/aca snornas, and applied it to saccharomyces cerevisiae. we report here results of extending our method to screen for h/aca rnas in multiple large genomes of related species, and apply it to the human, mouse, and rat genomes. because of the 250-fold larger search space compared to s. cerevisiae, significant enhancem ...200616373490
dj-1 interacts with hipk1 and affects h2o2-induced cell death.dj-1 is a novel oncogene and causative gene for the familial form of parkinson's disease (pd). dj-1 has multiple functions, including anti-oxidative stress by eliminating reactive oxygen species (ros) and transcriptional regulation as a coactivator, and loss of these functions are thought to trigger the onset of pd. the mechanism underlying the prevention of cell death by dj-1 is, however, not clear. in this study, we found that dj-1 directly bound to homeodomaininteracting protein kinase 1 (hip ...200616390825
candida albicans ecm33p is important for normal cell wall architecture and interactions with host cells.candida albicans ecm33 encodes a glycosylphosphatidylinositol-linked cell wall protein that is important for cell wall integrity. it is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis. to identify potential mechanisms through which ecm33p contributes to virulence, we investigated the interactions of c. albicans ecm33delta mutants with endothelial cells and the fadu oral epithelial cell line in vitro. the growth rate of blastospores of strains cont ...200616400176
the carbohydrate-recognition domain of dectin-2 is a c-type lectin with specificity for high mannose.we examined the carbohydrate-binding potential of the c-type lectin-like receptor dectin-2 (clecf4n). the carbohydrate-recognition domain (crd) of dectin-2 exhibited cation-dependent mannose/fucose-like lectin activity, with an ic(50) for mannose of approximately 20 mm compared to an ic(50) of 1.5 mm for the macrophage mannose receptor when assayed by similar methodology. the extracellular domain of dectin-2 exhibited binding to live candida albicans and the saccharomyces-derived particle zymosa ...200616423983
obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast.storage and degradation of triglycerides are essential processes to ensure energy homeostasis and availability of precursors for membrane lipid synthesis. recent evidence suggests that an emerging class of enzymes containing a conserved patatin domain are centrally important players in lipid degradation. here we describe the identification and characterization of a major triglyceride lipase of the adipose triglyceride lipase/brummer family, tgl4, in the yeast saccharomyces cerevisiae. eliminatio ...200616267052
the flo8 transcription factor is essential for hyphal development and virulence in candida albicans.the transcription factor flo8 is essential for filamentous growth in saccharomyces cerevisiae and is regulated under the camp/protein kinase a (pka) pathway. to determine whether a similar pathway/regulation exists in candida albicans, we have cloned c. albicans flo8 by its ability to complement s. cerevisiae flo8. deleting flo8 in c. albicans blocked hyphal development and hypha-specific gene expression. the flo8/flo8 mutant is avirulent in a mouse model of systemic infection. genome-wide trans ...200616267276
the murine dnali1 gene encodes a flagellar protein that interacts with the cytoplasmic dynein heavy chain 1.axonemal dyneins are large motor protein complexes generating the force for the movement of eukaryotic cilia and flagella. disruption of axonemal dynein function leads to loss of ciliary motility and can result in male infertility or lateralization defects. here, we report the molecular analysis of a murine gene encoding the dynein axonemal light intermediate chain dnali1. the dnali1 gene is localized on chromosome 4 and consists of six exons. it is predominantly expressed within the testis but ...200616496424
isolates of candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses.three distinct isolates of candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. patterns of infection differed significantly between both yeasts and mouse strains. systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible cba/cah mice than in the resistant balb/c ...200616503182
targeting of c-terminal binding protein (ctbp) by arf results in p53-independent apoptosis.arf encodes a potent tumor suppressor that antagonizes mdm2, a negative regulator of p53. arf also suppresses the proliferation of cells lacking p53, and loss of arf in p53-null mice, compared with arf or p53 singly null mice, results in a broadened tumor spectrum and decreased tumor latency. to investigate the mechanism of p53-independent tumor suppression by arf, potential interacting proteins were identified by yeast two-hybrid screen. the antiapoptotic transcriptional corepressor c-terminal ...200616508011
differential localization of complement component 3 within the capsular matrix of cryptococcus neoformans.the polysaccharide capsule of cryptococcus neoformans is a powerful activator of the complement system. the goal of the present study was to assess serum and cellular variables that influence the sites for c3 binding within the capsular matrix. confocal microscopy using fluorophore-labeled polyclonal anti-c3 and anticapsular monoclonal antibodies and rosetting of fluorescent microspheres coated with anti-c3 were used to identify sites of c3 binding relative to the capsular edge. the results show ...200616714537
separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression.separase is a protease whose liberation from its inhibitory chaperone securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit. we have created conditional knockout alleles of the mouse separase and securin genes. deletion of both copies of separase but not securin causes embryonic lethality. loss of securin reduces separase activity because deletion of just one copy of the separase gene is lethal to embryos lacking securin. in embryonic fibr ...200616533945
structures of eukaryotic ribonucleotide reductase i define gemcitabine diphosphate binding and subunit assembly.ribonucleotide reductase (rnr) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. crucial for rapidly dividing cells, rnr is a target for cancer therapy. in eukaryotes, rnr comprises a heterooligomer of alpha(2) and beta(2) subunits. rnr1, the alpha subunit, contains regulatory and catalytic sites; rnr2, the beta subunit (in yeast, a heterodimer of rnr2 and rnr4), houses the diferric-tyrosyl radical crucial for catalysis. here, we present three x-ray structures ...200616537480
mutations in sox2 cause anophthalmia-esophageal-genital (aeg) syndrome.we report heterozygous, loss-of-function sox2 mutations in three unrelated individuals with anophthalmia-esophageal-genital (aeg) syndrome. one previously reported case [rogers, r.c. (1988) unknown cases. proceedings of the greenwood genetic center. 7, 57.] has a 2.7 mb deletion encompassing sox2 and associated with a cryptic translocation t(3;7)(q28;p21.3). the deletion and translocation breakpoints on chromosome 3q are >8.6 mb apart and both chromosome rearrangements have occurred de novo. ano ...200616543359
transport characteristics of mammalian rh and rh glycoproteins expressed in heterologous systems.the development and use of heterologous expression systems is critical for deciphering the function of mammalian rh and rh-glycoproteins. the studies here use xenopus oocytes, well known for their ability to readily traffic and express difficult membrane proteins, and s. cerevisiae wild-type strains and mutants that are defective in ammonium transport. data obtained in both of these expression systems revealed that mammalian rh-glycoprotein-mediated transport (rhag, rhbg, and rhcg) is an electro ...200616563829
chmp5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis.charged mvb protein 5 (chmp5) is a coiled coil protein homologous to the yeast vps60/mos10 gene and other escrt-iii complex members, although its precise function in either yeast or mammalian cells is unknown. we deleted the chmp5 gene in mice, resulting in a phenotype of early embryonic lethality, reflecting defective late endosome function and dysregulation of signal transduction. chmp5-/- cells exhibit enlarged late endosomal compartments that contain abundant internal vesicles expressing pro ...200616567502
oog1, an oocyte-specific protein, interacts with ras and ras-signaling proteins during early embryogenesis.we previously identified an oocyte-specific gene, oogenesin 1 (oog1), that encodes 326 amino acids containing a leucine zipper structure and a leucine-rich repeat. in the present study, to identify the interacting proteins of oog1, we performed a yeast two-hybrid screening using a gv-oocyte cdna library and found that ral guanine nucleotide dissociation stimulator (ralgds) is the binding partner of oog1. coimmunoprecipitation assay confirmed the interaction between oog1 and ralgds proteins. colo ...200616580637
the high-mobility-group domain of sox proteins interacts with dna-binding domains of many transcription factors.sox proteins are widely believed to team up with other transcription factors as partner proteins to perform their many essential functions during development. in this study, yeast two-hybrid screens identified transcription factors as a major group of interacting proteins for sox8 and sox10. interacting transcription factors were very similar for these two group e sox proteins and included proteins with different types of dna-binding domains, such as homeodomain proteins, zinc finger proteins, b ...200616582099
selective regulation of il-10 signaling and function by zymosan.balanced activity of pro- and anti-inflammatory cytokines during innate immune responses is required to allow effective host defense while avoiding tissue damage and autoimmunity. induction of cytokine production after recognition of pathogen-associated molecular patterns (pamps) by innate immune cells has been well demonstrated, but modulation of cytokine function by pamps is not well understood. in this study we show that stimulation of macrophages with zymosan, which contains pamps derived fr ...200616585572
identification of the key lmo2-binding determinants on ldb1.the overexpression of lim-only protein 2 (lmo2) in t-cells, as a result of chromosomal translocations, retroviral insertion during gene therapy, or in transgenic mice models, leads to the onset of t-cell leukemias. lmo2 comprises two protein-binding lim domains that allow lmo2 to interact with multiple protein partners, including lim domain-binding protein 1 (ldb1, also known as clim2 and nli), an essential cofactor for lmo proteins. sequestration of ldb1 by lmo2 in t-cells may prevent it bindin ...200616616188
a recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus.allelic exclusion ensures that individual b lymphocytes produce only one kind of antibody molecule. previous studies have shown that allelic exclusion of the mouse igkappa locus occurs by the combination of monoallelic silencing and a low level of monoallelic activation for rearrangement combined with a negative feedback loop blocking additional functional rearrangements. using yeast artificial chromosome-based single-copy isotransgenic mice, we have identified a cis-acting element that negative ...200616618599
p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation.p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. therefore, we evaluated the effect of p205 on the p53 and rb-dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro in a p53-dependent manner. in addition, p205 induces increased expression of rb, and binds directly ...200616458891
long inverted repeats in eukaryotic genomes: recombinogenic motifs determine genomic plasticity.inverted repeats are unstable motifs in a genome, having a causal relation to fragment rearrangements and recombination events. we have investigated long inverted repeats (lir) of > 30 bp in length in eukaryotic genomes to assess their contribution to genome stability. an algorithm was first designed for searching for lirs with < 2 kb internal spacers and >85% identity (degree of homology between repeat copies of a lir). there are much fewer lirs in yeast, fruitfly, pufferfish and chicken than i ...200616466723
paracoccin, a glcnac-binding lectin from paracoccidioides brasiliensis, binds to laminin and induces tnf-alpha production by macrophages.paracoccidioides brasiliensis components interact with host cells and can influence the pathogenesis of paracoccidioidomycosis (pcm). among the components released by p. brasiliensis, gp 43 and a heavily glycosylated antigen with mm>160 kda are the most recognized by serum antibodies from patients with pcm. in order to isolate the high mm glycoconjugate, we carried out affinity chromatography of a crude exoantigen preparation on immobilized jacalin. the bound fraction (jbe, jacalin binding exoan ...200616476564
regulation of cytoplasmic dynein atpase by lis1.mutations in lis1 cause classical lissencephaly, a developmental brain abnormality characterized by defects in neuronal positioning. over the last decade, a clear link has been forged between lis1 and the microtubule motor cytoplasmic dynein. substantial evidence indicates that lis1 functions in a highly conserved pathway with dynein to regulate neuronal migration and other motile events. yeast two-hybrid studies predict that lis1 binds directly to dynein heavy chains (sasaki et al., 2000; tai e ...200616481446
yogy: a web-based, integrated database to retrieve protein orthologs and associated gene ontology terms.we present yogy a web-based resource for orthologous proteins from nine eukaryotic organisms: homo sapiens, mus musculus, rattus norvegicus, arabidopsis thaliana, drosophila melanogaster, caenorhabditis elegans, plasmodium falciparum, schizosaccharomyces pombe and saccharomyces cerevisiae. using a gene name from any of these organisms as a query, this database provides comprehensive, combined information on orthologs in other species using data from five independent resources: kogs, inparanoid, ...200616845020
membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with c kinase 1 in a cerebellar purkinje neuron.the glutamate receptor delta2 subunit (glurdelta2) is selectively expressed in cerebellar purkinje neurons (pns) and is involved in the long-term depression (ltd). however, little is known about the mechanism of its action. acute expression of the wild-type glurdelta2 in the glurdelta2-deficient pn rescued the induction of ltd, suggesting the direct role of glurdelta2 in ltd. to identify the critical region of glurdelta2 necessary for ltd, we constructed and expressed various mutant glurdelta2 p ...200616597715
evidence from knockout mice against physiologically significant aquaporin 8-facilitated ammonia transport.aquaporin (aqp)8-facilitated transport of nh(3) has been suggested recently by increased nh(3) permeability in xenopus oocytes and yeast expressing human or rat aqp8. we tested the proposed roles of aqp8-facilitated nh(3) transport in mammalian physiology by comparative phenotype studies in wild-type vs. aqp8-null mice. aqp8-facilitated nh(3) transport was confirmed in mammalian cell cultures expressing rat or mouse aqp8, in which the fluorescence of a ph-sensing yellow fluorescent protein was m ...200616624991
suppressed disassembly of autolyzing p94/capn3 by n2a connectin/titin in a genetic reporter system.p94/calpain 3 is a skeletal muscle-specific member of the ca(2+)-regulated cytosolic cysteine protease family, the calpains. defective p94 protease activity originating from gene mutations causes a muscular dystrophy called calpainopathy, indicating the indispensability of p94 for muscle survival. because of the existence of the p94-specific regions is1 and is2, p94 undergoes very rapid and exhaustive autolysis. to elucidate the physiological relevance of this unique activity, the autolytic prof ...200616627476
p19ras interacts with and activates p73 by involving the mdm2 protein.p73beta is a structural and functional homologue of p53, a tumor suppressor gene. in this study, we identified a novel p73beta-binding protein, p19ras, by the yeast two-hybrid screening method. alternative splicing of the proto-oncogene h-ras pre-mrna has led to two distinct transcripts, p19ras and p21ras. in both endogenous and overexpressed systems, we confirmed that p19ras binds to full-length p73beta in vivo and in vitro. coexpression of p19ras with p73beta stimulated the transcriptional act ...200616436381
the swi/snf chromatin remodeling complex is essential for hyphal development in candida albicans.the ability of dimorphic transition between yeast and hyphal forms in candida albicans is one of the vital determinants for its pathogenicity and virulence. we isolated c. albicans swi1 as a suppressor of the invasive growth defect in a saccharomyces cerevisiae mutant. expression of c. albicans swi1 in s. cerevisiae partially complemented the growth defect of a swi1 mutant in the utilization of glycerol. swi1 is in a complex with snf2 in c. albicans, and both proteins are localized in the nucleu ...200616647065
sun1 interacts with nuclear lamin a and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton.nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (ne) proteins that share a conserved c-terminal sun (sad1/unc-84 homology) domain. analysis of caenorhabditis elegans mutants has implicated unc-84 in actin-mediated nuclear positioning by regulating ne anchoring of a giant actin-bindi ...200616648470
genetic structure and evolution of the vps25 family, a yeast escrt-ii component.vps25p is the product of yeast gene vps25 and is found in an endosomal sorting complex required for transport (escrt)-ii, along with vps22p and vps36p. this complex is essential for sorting of ubiquitinated biosynthetic and endosomal cargoes into endosomes.200616889659
the nuclear hormone receptor farnesoid x receptor (fxr) is activated by androsterone.farnesoid x receptor (fxr) uses bile acids as endogenous ligands. here, we demonstrate that androsterone, a metabolic product of testosterone, is also an fxr ligand. treatment of castrated male mice with androsterone induced expression of the fxr target gene small heterodimer partner (shp). in mouse aml-12 hepatocytes, chenodeoxycholic acid (cdca) or androsterone induced shp expression with a similar kinetic pattern. the fxr antagonist guggulsterone blocked the induction of shp by androsterone i ...200616675527
ptarget: a web server for predicting protein subcellular localization.the ptarget web server enables prediction of nine distinct protein subcellular localizations in eukaryotic non-plant species. predictions are made using a new algorithm [c. guda and s. subramaniam (2005) ptarget [corrected] a new method for predicting protein subcellular localization in eukaryotes. bioinformatics, 21, 3963-3969], which is primarily based on the occurrence patterns of location-specific protein functional domains in different subcellular locations. we have implemented a relational ...200616844995
a mouse trapp-related protein is involved in pigmentation.we identified a new spontaneous recessive mutation in the mouse, mhyp (mosaic hypopigmentation), in a screen for novel proviral integration sites in a multiple ecotropic provirus mapping stock. integration of an 8.4-kb retrovirus results in mosaic loss of coat pigment in mhyp homozygotes. patchy loss of pigmentation in the retinal pigmented epithelial layer of the eye with abnormal melanosomes is also evident. we mapped mhyp to mouse chromosome 7 and cloned the underlying gene. mhyp is a defect ...200616697553
nuclear pore complex assembly and maintenance in pom121- and gp210-deficient cells.so far, pom121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (npcs) within the lipid bilayer of the nuclear envelope (ne) and, thus, are excellent candidates for initiating the npc assembly process. indeed, we demonstrate that pom121 can recruit several nucleoporins, such as nup62 or nup358, to ectopic assembly sites. it thus appears to act as a nucleation site for the assembly of npc substructures. nonetheless, we observed functional npcs and intact nes in se ...200616702234
differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver x receptor-beta, and retinoid x receptor-alpha.administration of ammonium salts of perfluorooctanoate (pfoa) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (nr) peroxisome proliferator-activated receptor-alpha (pparalpha). due to its fatty acid structure, pfoa may activate other nrs, such as pparbeta, ppargamma, liver x receptor (lxr), or retinoid x receptor (rxr). in this study, the activation of human, mouse, and rat pparalpha, pparbeta, ppargamma, lxrbeta, and ...200616731579
integrin cytoplasmic domain-associated protein-1 (icap-1) interacts with the rock-i kinase at the plasma membrane.the integrin cytoplasmic domain-associated protein-1 (icap-1) binds via its c-terminal ptb (phosphotyrosine-binding) domain to the cytoplasmic tails of beta1 but not other integrins. using the yeast two-hybrid assay, we found that icap-1 binds the rock-i kinase, an effector of the rhoa gtpase. by coimmunoprecipitation we show that icap-1 and rock form complexes in cells and that icap-1 contains two binding sites for rock. in cells transfected with both icap-1 and rock, the proteins colocalized a ...200616741948
yke4 (yil023c) encodes a bidirectional zinc transporter in the endoplasmic reticulum of saccharomyces cerevisiae.yil023c encodes a member of the slc39a, or zip, family, which we refer to as yeast ke4 (yke4) after its mouse ortholog. yke4p was localized to the endoplasmic reticulum (er) membrane using yke4p-specific antiserum. yke4 is not an essential gene; however, deletion of yke4 resulted in a sensitivity to calcofluor white and poor growth at 36 degrees c on respiratory substrates containing high zinc. overexpression of transition metal transporters zrc1p and cot1p or the mouse orthologue mke4 in deltay ...200616760462
protein phosphatase 6 subunit with conserved sit4-associated protein domain targets ikappabepsilon.protein ser/thr phosphatases compose a ppp family that includes type-2 pp2a, pp4, and pp6, each with essential functions. the human pp6 gene rescues sit4(ts) mutants of saccharomyces cerevisiae, and sit4 phosphatase function depends on multiple sit4-associated protein (sap) subunits. we report here finding a saps sequence domain encoded in only a single gene each in schizosaccharomyces pombe, caenorhabditis elegans, and drosophila but in three distinct open reading frames in xenopus, mus musculu ...200616769727
differential gene expression by paracoccidioides brasiliensis in host interaction conditions: representational difference analysis identifies candidate genes associated with fungal pathogenesis.paracoccidioides brasiliensis causes infection by the host inhalation of airborne propagules of the mycelia phase of the fungus. these particles reach the lungs, and disseminate to virtually all organs. here we describe the identification of differentially expressed genes in studies of host-fungus interaction. we analyzed two cdna populations of p. brasiliensis, one obtained from infected animals and the other an admixture of fungus and human blood thus mimicking the hematologic events of the fu ...200616962356
saccharomyces boulardii inhibits erk1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against clostridium difficile toxin a-induced enteritis.saccharomyces boulardii (sb), a probiotic yeast, protects against intestinal injury and inflammation caused by a wide variety of enteric pathogens, including clostridium difficile. given the broad range of protective effects of sb in multiple gastrointestinal disorders, we hypothesize that sb modulates host signaling pathways involved in intestinal inflammatory responses. in this study, we found that sb culture supernatant (sbs) inhibits interleukin-8 production induced by c. difficile toxin a o ...200616816386
control of transcription factor activity and osteoblast differentiation in mammalian cells using an evolved small-molecule-dependent intein.inteins are naturally occurring protein elements that catalyze their own excision from within a larger protein together with the ligation of the flanking "extein" sequences. previously we reported the directed evolution of an intein-based molecular switch in which intein splicing in yeast cells was made dependent on the cell-permeable small molecule 4-hydroxytamoxifen (4-ht). here we show that these evolved inteins are effective means of rendering protein function and biological signaling pathwa ...200616819890
inositol phosphate metabolomics: merging genetic perturbation with modernized radiolabeling methods.recent discoveries that provide a link between inositol phosphate (ip) signaling and fundamental cellular processes evoke many exciting new hypotheses about ip function, and underscore the importance of understanding how ip synthesis is regulated. central to studies of ip metabolism is the essential development of efficient, fast, and reproducible methods for quantitative analysis of ips in systems ranging from simple cell cultures to more complex tissues and whole organisms. additionally, in ma ...200616829132
whirlin complexes with p55 at the stereocilia tip during hair cell development.hearing in mammals depends upon the proper development of actin-filled stereocilia at the hair cell surface in the inner ear. whirlin, a pdz domain-containing protein, is expressed at stereocilia tips and, by virtue of mutations in the whirlin gene, is known to play a key role in stereocilia development. we show that whirlin interacts with the membrane-associated guanylate kinase (maguk) protein, erythrocyte protein p55 (p55). p55 is expressed in outer hair cells in long stereocilia that make up ...200616829577
inhibition of atf4 transcriptional activity by fiat/gamma-taxilin modulates bone mass accrual.the basic domain-leucine zipper protein, activating transcription factor 4 (atf4), was recently shown to control key aspects of osteoblast biology. atf4 regulates the timely onset of osteoblast differentiation, the synthesis of type i collagen, and the transcription of the osteocalcin and rankl (receptor activator of nfkappa-b ligand) genes. accordingly, the levels and activity of atf4 are under tight control through mechanisms that include protein stability and phosphorylation. we have uncovere ...200616831913
mammalian tak1 activates snf1 protein kinase in yeast and phosphorylates amp-activated protein kinase in vitro.the snf1/amp-activated protein kinase (ampk) family is important for metabolic regulation and is highly conserved from yeast to mammals. the upstream kinases are also functionally conserved, and the ampk kinases lkb1 and ca2+/calmodulin-dependent protein kinase kinase activate snf1 in mutant yeast cells lacking the native snf1-activating kinases, sak1, tos3, and elm1. here, we exploited the yeast genetic system to identify members of the mammalian ampk kinase family by their function as snf1-act ...200616835226
resolution of chiasmata in oocytes requires separase-mediated proteolysis.in yeast, resolution of chiasmata in meiosis i requires proteolytic cleavage along chromosome arms of cohesin's rec8 subunit by separase. since activation of separase by the anaphase-promoting complex (apc/c) is supposedly not required for meiosis i in xenopus oocytes, it has been suggested that animal cells might resolve chiasmata by a separase-independent mechanism related to the so-called "prophase pathway" that removes cohesin from chromosome arms during mitosis. by expressing cre recombinas ...200616839882
snx5, as a mind bomb-binding protein, is expressed in hematopoietic and endothelial precursor cells in zebrafish.notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. previously, we identified a novel component of the notch signaling pathway in zebrafish, mind bomb, which encodes an e3 ubiquitin ligase essential for notch signal activation. further studies showed that mind bomb(-/-) mouse embryos exhibited pan-notch phenotypes in various tissues, suggesting that mind bomb function is conserved in mammals. therefore we sought to understand the variou ...200616857196
the coiled-coil protein shrub controls neuronal morphogenesis in drosophila.the diversity of neuronal cells, especially in the size and shape of their dendritic and axonal arborizations, is a striking feature of the mature nervous system. dendritic branching is a complex process, and the underlying signaling mechanisms remain to be further defined at the mechanistic level. here we report the identification of shrub mutations that increased dendritic branching. single-cell clones of shrub mutant dendritic arborization (da) sensory neurons in drosophila larvae showed ecto ...200616713958
rev1 protein interacts with pcna: significance of the rev1 brct domain in vitro and in vivo.rev1 protein, a eukaryotic member of the y family of dna polymerases, is involved in the tolerance of dna damage by translesion dna synthesis. it is unclear how rev1 is recruited to replication foci in cells. here, we report that mouse rev1 can bind directly to pcna and that monoubiquitylation of pcna enhances this interaction. the interaction between rev1 protein and pcna requires a functional brct domain located near the n terminus of the former protein. deletion or mutational inactivation of ...200616857592
glucose as a regulator of eukaryotic gene transcription.glucose has essential metabolic roles as both a fuel for energy and a substrate for the biosynthesis of cell components. because of its central importance, many cells have evolved mechanisms to sense glucose levels in their environment and to adapt the expression of their genetic information to glucose availability. this glucose signaling is vital in mammalian cells where derangements in glucose utilization might contribute to conditions such as obesity and type 2 diabetes. two crucial issues st ...200516269245
mouse ache binds in vivo to domain iv of laminin-1beta.functions of acetylcholinesterase (ache) other than hydrolysis of acetylcholine, e.g. related to cell differentiation, synaptogenesis, neuronal signaling and diseases are well documented, but mechanisms supporting them are not understood. therefore, we searched for ache ligands in the central nervous system using a yeast two-hybrid screen (y2h). 18 independent candidates were identified. one of the membrane or extracellular proteins was laminin-1, an extracellular matrix protein involved in neur ...200516429555
mycobacterium tuberculosis lipoarabinomannan-mediated irak-m induction negatively regulates toll-like receptor-dependent interleukin-12 p40 production in macrophages.mannose-capped lipoarabinomannans (man-lams) are members of the repertoire of mycobacterium tuberculosis modulins that the bacillus uses to subvert the host innate immune response. interleukin-12 (il-12) production is critical for mounting an effective immune response by the host against m. tuberculosis. we demonstrate that man-lam inhibits il-12 p40 production mediated by subsequent challenge with lipopolysaccharide (lps). man-lam inhibits lps-induced il-12 p40 expression in an il-10-independen ...200516263713
nuclear translocation of alphan-catenin by the novel zinc finger transcriptional repressor zasc1.alpha-catenins anchor the transmembrane cell-cell adhesion molecule e-cadherin indirectly to the actin cytoskeleton through interaction with beta-catenin or plakoglobin. three different alpha-catenins are known at present: alphae-, alphat-, and alphan-catenin. despite their different expression patterns, no functional differences between the alpha-catenins are known. in a yeast two-hybrid screening with alphan-catenin as bait, we identified the cys(2)-his2 zinc finger protein zasc1. the mrna and ...200516182284
multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane.polypeptides that fail to pass quality control in the endoplasmic reticulum (er) are dislocated from the er membrane to the cytosol where they are degraded by the proteasome. derlin-1, a member of a family of proteins that bears homology to yeast der1p, was identified as a factor that is required for the human cytomegalovirus us11-mediated dislocation of class i mhc heavy chains from the er membrane to the cytosol. derlin-1 acts in concert with the aaa atpase p97 to remove dislocation substrate ...200516186509
a novel mammalian retromer component, vps26b.the mammalian retromer protein complex, which consists of three proteins--vps26, vps29, and vps35--in association with members of the sorting nexin family of proteins, has been implicated in the trafficking of receptors and their ligands within the endosomal/lysosomal system of mammalian cells. a bioinformatic analysis of the mouse genome identified an additional transcribed paralog of the vps26 retromer protein, which we termed vps26b. no paralogs were identified for vps29 and vps35. phylogenet ...200516190980
suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering rna targeting kitenin, a metastasis-enhancing protein.kitenin promotes invasion of mouse colon adenocarcinoma (ct-26) cells in vivo. here, we studied the effects of in vivo kitenin ablation on established tumors by using psuper vectors (psuper-kitenin) producing short interfering rna (sirna). when psuper-kitenin was given weekly or semiweekly for 1 month into tail vein of syngeneic mice that have established colon tumors, tumor size regressed markedly and metastases were inhibited. in mice injected with psuper-kitenin, serum interleukin-2 (il-2) an ...200516204073
implementing the ihop concept for navigation of biomedical literature.the world wide web has profoundly changed the way in which we access information. searching the internet is easy and fast, but more importantly, the interconnection of related contents makes it intuitive and closer to the associative organization of human memory. however, the information retrieval tools currently available to researchers in biology and medicine lag far behind the possibilities that the layman has come to expect from the internet.200516204114
selection of optimal host strain for molecular pathogenesis studies on cryptococcus gattii.encapsulated yeast, cryptococcus gattii (cg) is a primary and emerging fungal pathogen in north america. it has a predilection for invading the central nervous system of both healthy and immunocompromised humans and animals. recently, we initiated molecular pathogenesis studies in cg strain nih444 (atcc 32609). in this report, we compared the biology and pathogenic potential of nih444 to those of wm276, an australian environmental isolate that is being used for the whole genome-sequencing projec ...200516205969
wox1 is essential for tumor necrosis factor-, uv light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53.ww domain-containing oxidoreductase wox1, also named wwox or for, undergoes tyr33 phosphorylation at its first n-terminal ww domain and subsequent nuclear translocation in response to sex steroid hormones and stress stimuli. the activated wox1 binds tumor suppressor p53, and both proteins may induce apoptosis synergistically. functional suppression of wox1 by antisense mrna or a dominant negative abolishes p53-mediated apoptosis. here, we determined that uv light, anisomycin, etoposide, and hypo ...200516219768
the m-aaa protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria.aaa proteases comprise a conserved family of membrane bound atp-dependent proteases that ensures the quality control of mitochondrial inner-membrane proteins. inactivation of aaa proteases causes pleiotropic phenotypes in various organisms, including respiratory deficiencies, mitochondrial morphology defects, and axonal degeneration in hereditary spastic paraplegia (hsp). the molecular basis of these defects, however, remained unclear. here, we describe a regulatory role of an aaa protease for m ...200516239145
frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells.deficiency of the frataxin mrna alters the transcriptome, triggering neuro- and cardiodegeneration in friedreich's ataxia. we microarrayed murine frataxin-deficient heart tissue, liver tissue and cardiocytes and observed a transcript down-regulation to up-regulation ratio of nearly 2:1 with a mitochondrial localization of transcriptional changes. combining all mouse and human microarray data for frataxin-deficient cells and tissues, the most consistently decreased transcripts were mitochondrial ...200516239244
lactate utilization in mitochondria prevents bax cytotoxicity in yeast kluyveromyces lactis.in a search for the physiological conditions able to suppress the disruption of electron transport through the inner mitochondrial membrane induced by bax, we found that respiratory substrate - lactate completely abolished bax toxicity in yeast kluyveromyces lactis. the effect of lactate was dependent on the presence of cytochrome c, as no effect was observed in the cytochrome c null strain. the investigation of lactate effect on markers of bax toxicity showed that: (i) oxidation of lactate did ...200516150448
development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13.lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota ("microflora"). antibiotics also lead to overgrowth of the yeast candida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. we have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable i ...200515618138
yeast two-hybrid screens imply that ggnbp1, ggnbp2 and oaz3 are potential interaction partners of testicular germ cell-specific protein ggn1.gametogenetin (ggn) is a testicular germ cell-specific gene specifically expressed from late pachytene spermatocytes through round spermatids. the function of gametogenetin protein 1 (ggn1) remains unknown. here, we used the yeast two-hybrid approach to look for more ggn1 interacting proteins. we found that gametogenetin binding protein 1 (ggnbp1), gametogenetin binding protein 2 (ggnbp2) and ornithine decarboxylase antizyme 3 (oaz3) were potential ggn1 interaction partners. we determined the re ...200515642376
a modified tandem affinity purification tag technique for the purification of protein complexes in mammalian cells.the tandem affinity purification (tap) tag technique has been used with success to identify under nondenaturing conditions protein complexes in yeast. the technique can be used in mammalian cells, but we found that the original technique does not yield enough recovery for the identification of proteins when mammalian cells growing in monolayer have to be used. we present here a modified tap tag technique that allows sufficient recovery of proteins from mouse fibroblasts growing in monolayer cult ...200515602769
online predicted human interaction database.high-throughput experiments are being performed at an ever-increasing rate to systematically elucidate protein-protein interaction (ppi) networks for model organisms, while the complexities of higher eukaryotes have prevented these experiments for humans.200515657099
candida albicans protein kinase cahsl1p regulates cell elongation and virulence.saccharomyces cerevisiae hsl1p is a ser/thr protein kinase that regulates cell morphology. we identified candida albicans cahsl1 and analysed its function in c. albicans. cells lacking cahsl1p exhibited filamentous growth under yeast growth conditions with the filaments elongating more quickly than did those of the wild type under hyphal growth conditions, suggesting that it plays a role in the suppression of cell elongation. green fluorescent protein-tagged cahsl1p colocalized with a septin com ...200515659158
the wd-40 repeat motif of lgl tumor suppressor proteins associated with salt tolerance and temperature sensitivity.we have recently identified mammalian homologues of lethal giant larvae (lgl) tumor suppressor gene, rat rgl-1 and bovine bgl-1, and demonstrated that they can complement yeast double mutants lacking sop1 and sop2, yeast homologues of lgl. these gene products are capable of regulating cellular viability in restrictive salt and temperature environments. since lgl family members contain the wd-40 repeat motif, we investigated its cellular functions using mouse homologue mgl-1 in the absence of sop ...200515882966
pias1 interaction and sumoylation of metabotropic glutamate receptor 8.group iii presynaptic metabotropic glutamate receptors (mglurs) play a central role in regulating presynaptic activity through g-protein effects on ion channels and signal transducing enzymes. like all class c g-protein-coupled receptors, mglur8 has an extended intracellular c-terminal domain (ctd) presumed to allow for modulation of downstream signaling. in a yeast two-hybrid screen of an adult rat brain cdna library with the ctds of mglur8a and 8b (mglur8-c) as baits, we identified sumo1 and f ...200516144832
genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine.apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with parkinson's disease. both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. in the present review, we discuss recent studies from our laboratory i ...200515962173
a novel splice variant of human xrn2 gene is mainly expressed in blood leukocyte.the xrn2 gene (xrn2a) is the human homologue of the saccharomyces cerevisiae rat1 gene, which encodes a nuclear 5'-->3' exoribonuclease, and is essential for rna metabolism and cell viability. xrn2p/rat1p, product of xrn2/rat1 gene, functions in the mrna degradation and processing of rrnas and small nucleolar rnas (snornas) in the nucleus. here we describe the cloning and characterization of a novel splice variant of the human xrn2 gene (xrn2b). the 3271-bp cdna encodes a putative protein with 9 ...200516147866
an alliance between ras gtpase-activating protein, filamin c, and ras gtpase-activating protein sh3 domain-binding protein regulates myocyte growth.we have previously reported that ras gtpase-activating protein (rasgap) is involved in a pathway that regulates total cellular mrna and protein synthesis in cardiac myocytes. a yeast two-hybrid screen resulted in identification of filamin c (fln-c) as one of its targets. knockdown of rasgap or fln-c, or severing their interaction, resulted in down-regulation of the rna polymerase ii kinase, cyclin-dependent kinase 7 (cdk7). this appeared to be provoked by the release of cdk7 mrna from rasgap sh3 ...200515886195
Displaying items 501 - 600 of 2282