Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch.the p62 protein functions as a scaffold in signaling pathways that lead to activation of nf-kappab and is an important regulator of osteoclastogenesis. mutations affecting the receptor activator of nf-kappab signaling axis can result in human skeletal disorders, including those identified in the c-terminal ubiquitin-associated (uba) domain of p62 in patients with paget disease of bone. these observations suggest that the disease may involve a common mechanism related to alterations in the ubiqui ...200818083707
cta4 transcription factor mediates induction of nitrosative stress response in candida albicans.this work has identified regulatory elements in the major fungal pathogen candida albicans that enable response to nitrosative stress. nitric oxide (no) is generated by macrophages of the host immune system and commensal bacteria, and the ability to resist its toxicity is one adaptation that promotes survival of c. albicans inside the human body. exposing c. albicans to no induces upregulation of the flavohemoglobin yhb1p. this protein confers protection by enzymatically converting no to harmles ...200818083829
mitochondrial iba57p is required for fe/s cluster formation on aconitase and activation of radical sam enzymes.a genome-wide screen for saccharomyces cerevisiae iron-sulfur (fe/s) cluster assembly mutants identified the gene iba57. the encoded protein iba57p is located in the mitochondrial matrix and is essential for mitochondrial dna maintenance. the growth phenotypes of an iba57delta mutant and extensive functional studies in vivo and in vitro indicate a specific role for iba57p in the maturation of mitochondrial aconitase-type and radical sam fe/s proteins (biotin and lipoic acid synthases). maturatio ...200818086897
rack1 regulates the cell surface expression of the g protein-coupled receptor for thromboxane a(2).we used the yeast two-hybrid system to screen for proteins that interact with the c-terminus of the beta isoform of the thromboxane a(2) receptor (tpbeta). this screen identified receptor for activated c-kinase 1 (rack1) as a new tpbeta-interacting protein. here, we show that rack1 directly binds to the c-terminus and the first intracellular loop of tpbeta. the tpbeta-rack1 association was further confirmed by co-immunoprecipitation studies in hek293 cells and was not modulated by stimulation of ...200818088317
imaging of lipid biosynthesis: how a neutral lipid enters lipid droplets.the biosynthesis and storage of triglyceride (tg) is an important cellular process conserved from yeast to man. most mammalian cells accumulate tg in lipid droplets, most prominent in adipocytes, which are specialized to store large amounts of the tg over long periods. in this study, we followed tg biosynthesis and targeting by fluorescence imaging in living 3t3-l1 adipocytes and cos7 fibroblasts. key findings were (i) not only tg but also its direct metabolic precursor diacylglycerol, dg, accum ...200818088320
a two-hybrid yeast assay to quantify the effects of xenobiotics on thyroid hormone-mediated gene expression.over the last few years, increasing evidence has become available that some chemicals may have thyroid hormone- disrupting potencies. the effects exerted via thyroid hormone receptors (tr) have not been studied thoroughly. the present study investigates chemical thyroid hormone disruption at the level of tr functioning. to this end the (ant)agonistic action of a series of xenobiotics was tested in the newly developed yeast two-hybrid assay. this assay makes use of recombined trbeta gene and repo ...200818092857
control of estradiol-directed gene transactivation by an intracellular estrogen-binding protein and an estrogen response element-binding protein.new world primates exhibit a form of resistance to estrogens that is associated with overexpression of an estrogen response element (ere)-binding protein (ere-bp) and an intracellular estradiol (e(2))-binding protein (iebp). both proteins suppress e(2)-mediated transcription when overexpressed in estrogen receptor-alpha (eralpha)-positive cells. although ere-bp acts as a competitor for ere occupancy by liganded eralpha, the function of iebp and its human homolog, heat-shock protein 27 (hsp27), i ...200818096692
a small protein that fights fungi: afp as a new promising antifungal agent of biotechnological value.as fungal infections are becoming more prevalent in the medical or agricultural fields, novel and more efficient antifungal agents are badly needed. within the scope of developing new strategies for the management of fungal infections, antifungal compounds that target essential fungal cell wall components are highly preferable. ideally, newly developed antimycotics should also combine major aspects such as sustainability, high efficacy, limited toxicity and low costs of production. a naturally d ...200818066545
effects of the g376e and g157d mutations on the stability of yeast enolase--a model for human muscle enolase deficiency.the first known human enolase deficiency was reported in 2001 [comi gp, fortunato f, lucchiari s, bordoni a, prelle a, jann s, keller a, ciscato p, galbiati s, chiveri l et al. (2001) ann neurol50, 202-207]. the subject had inherited two mutated genes for beta-enolase. these mutations changed glycine 156 to aspartate and glycine 374 to glutamate. in order to study the effects of these changes on the structure and stability of enolase, we have introduced the corresponding changes (g157d and g376e ...200818070103
colocalization of mcm8 and mcm7 with proteins involved in distinct aspects of dna replication.minichromosome maintenance (mcm) proteins are essential for dna replication in eukaryotes. a subcomplex of the mcm2-7 family members, initially characterized in yeast, is thought to serve as a eukaryotic dna replicative helicase. mcm8 is a new family member, not present in yeast, which may function alone or with other family members in aspects of dna metabolism, including replication initiation and elongation. through the use of chromatin immunoprecipitation, we find that mcm8, like mcm7, coloca ...200818072282
molecular identification of pathogenic fungi.systemic fungal infections represent a major cause of morbidity and mortality in immunocompromised patients. the ever-increasing number of yeast species associated with human infections that are not covered by conventional identification kits, and the fact that moulds isolated from deep infections are frequently impossible to identify using classical methods due to lack of sporulation, has driven the need for rapid, robust molecular identification techniques. we recently developed a rapid method ...200818063605
red clover isoflavones biochanin a and formononetin are potent ligands of the human aryl hydrocarbon receptor.aryl hydrocarbon receptor (ahr) activation affects the cell cycle and drives cells to apoptosis. thus, selective ahr modulators (sahrms) have previously been implicated in cancer therapy and prevention, particularly for hormone-dependent cancers. in the present study, isoflavones a remedy used to ameliorate menopausal complaints were tested for their potential in transactivating ahr in order to investigate the biological function of red clover isoflavones. the results were compared to the transa ...200818060767
the leukemogenic calm/af10 fusion protein alters the subcellular localization of the lymphoid regulator ikaros.the t(10;11)(p13;q14) translocation leads to the fusion of the calm and af10 genes. this translocation can be found as the sole cytogenetic abnormality in acute lymphoblastic leukemia, acute myeloid leukemia and in malignant lymphomas. the expression of calm/af10 in primary murine bone marrow cells results in the development of an aggressive leukemia in a murine bone marrow transplantation model. using a yeast two-hybrid screen, we identified the lymphoid regulator ikaros as an af10 interacting ...200818037964
transcription processing at 1,n2-ethenoguanine by human rna polymerase ii and bacteriophage t7 rna polymerase.the dna lesion 1,n(2)-ethenoguanine (1,n(2)-epsilon g) is formed endogenously as a by-product of lipid peroxidation or by reaction with epoxides that result from the metabolism of the industrial pollutant vinyl chloride, a known human carcinogen. dna replication past 1,n(2)-epsilon g and site-specific mutagenesis studies on mammalian cells have established the highly mutagenic and genotoxic properties of the damaged base. however, there is as yet no information on the processing of this lesion d ...200818022639
involvement of ymer in suppression of nf-kappab activation by regulated interaction with lysine-63-linked polyubiquitin chain.it is known that the cytoplasmic zinc finger protein a20 functionally dampens inflammatory signals and apoptosis via inhibition of nf-kappab activation and biochemically acts as a unique ubiquitin-modifying protein with deubiquitinating activity and ubiquitin ligase activity. however, the molecular mechanisms of a20-modulated signal transduction that influence normal immune responses or tumor immunity have not been fully elucidated. using a yeast two-hybrid system to search for proteins interact ...200818029035
the role of glcnac in formation and function of extracellular matrices.n-acetylglucosamine (glcnac) is an abundant hexose that as a monomer or as part of macromolecules plays multiple roles in eukaryotic cells. especially as a residue of oligo- and polysaccharides and conjugated with lipids and proteins, glcnac contributes to the function and architecture of extracellular matrices. several human disorders caused by mutations in genes coding for enzymes dealing with glcnac have been identified. however, molecular aspects of their clinical picture are laborious to in ...200818032081
cytochrome p450s in the development of target-based anticancer drugs.enzymes of the cytochrome p450 (cyp) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. in new drug discovery research, recombinant (human) cyps are also used for identifying active or inactive metabolites that could lead to increased potency or toxicity of a molecule. in addition, cyp inhibition by anticancer drugs might lead to adverse drug reactions, multiple-drug resistance, and drug-drug interactions. during the discovery and p ...200818053638
localization of mouse mitochondrial sirt proteins: shift of sirt3 to nucleus by co-expression with sirt5.yeast silent information regulator 2 (sir2) is involved in extension of yeast longevity by calorie restriction, and sirt3, sirt4, and sirt5 are mammalian homologs of sir2 localized in mitochondria. we have investigated the localization of these three sirt proteins of mouse. sirt3, sirt4, and sirt5 proteins were localized in different compartments of the mitochondria. when sirt3 and sirt5 were co-expressed in the cell, localization of sirt3 protein changed from mitochondria to nucleus. these resu ...200818054327
nf-kappab-inducing kinase phosphorylates and blocks the degradation of down syndrome candidate region 1.down syndrome, the most frequent genetic disorder, is characterized by an extra copy of all or part of chromosome 21. down syndrome candidate region 1 (dscr1) gene, which is located on chromosome 21, is highly expressed in the brain of down syndrome patients. although its cellular function remains unknown, dscr1 expression is linked to inflammation, angiogenesis, and cardiac development. to explore the functional role of dscr1 and the regulation of its expression, we searched for novel dscr1-int ...200818056702
the pentatricopeptide repeats present in pet309 are necessary for translation but not for stability of the mitochondrial cox1 mrna in yeast.pet309 is a protein essential for respiratory growth. it is involved in translation of the yeast mitochondrial cox1 gene, which encodes subunit i of the cytochrome c oxidase. pet309 is also involved in stabilization of the cox1 mrna. mutations in a similar human protein, lrp130, are associated with leigh syndrome, where cytochrome c oxidase activity is affected. the sequence of pet309 reveals the presence of at least seven pentatricopeptide repeats (pprs) located in tandem in the central portion ...200818039654
characterization of secreted recombinant toxoplasma gondii surface antigen 2 (sag2) heterologously expressed by the yeast pichia pastoris.the surface antigen 2 (sag2) gene of the protozoan parasite, toxoplasma gondii, was cloned and extracellularly expressed in the yeast pichia pastoris. the effectiveness of the secreted recombinant sag2 (rsag2-s) as a serodiagnosis reagent was assessed by western blots and elisa. in the western blot assay, rsag2-s reacted with all toxoplasma-antibody positive human serum samples but not with toxoplasma-negative samples. in the elisa, rsag2-s yielded sensitivity rates ranging from 80% (igg negativ ...200818043869
derlin-1 and p97/valosin-containing protein mediate the endoplasmic reticulum-associated degradation of human v2 vasopressin receptors.the endoplasmic reticulum-associated degradation (erad), the main quality control pathway of the cell, is crucial for the elimination of unfolded or misfolded proteins. several diseases are associated with the retention of misfolded proteins in the early secretory pathway. among them is x-linked nephrogenic diabetes insipidus, caused by mutations in the gene encoding the v2 vasopressin receptor (v2r). we studied the degradation pathways of three intracellularly retained v2r mutants with differen ...200818048502
efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases.under conditions of oxidative stress, the formamidopyrimidine lesions (fapyg and fapya) are formed in competition with the corresponding 8-oxopurines (og and oa) from a common intermediate. in order to reveal features of the repair of these lesions, and the potential contribution of repair in mitigating or exacerbating the mutagenic properties of fapy lesions, their excision by three glycosylases, fpg, hogg1 and ntg1, was examined in various base pair contexts under single-turnover conditions. f ...200818154319
a family of eukaryotic lysophospholipid acyltransferases with broad specificity.the budding yeast ale1 gene encodes a lysophospholipid acyltransferase (lplat) with broad specificity. we show that yeast lplat (sclplat) belongs to a distinct protein family that includes human mboat1, mboat2, mboat4, and several closely related proteins from other eukaryotes. we further show that two plant proteins within this family, the arabidopsis proteins atlplat1 and atlplat2, possess lysophospholipid acyltransferase activities similar to sclplat. we propose that other members of this pro ...200818154737
cryptococcosis masquerading as a tuboovarian abscess.this report describes a 25-year-old human immunodeficiency virus- seropositive patient who initially presented with clinical features of a tuboovarian abscess. after a poor response to antibiotic therapy, laparotomy and excision of a right-sided, unilocular, pseudocystic ovarian mass measuring 140 x 80 x 60 mm were undertaken. mucoid gelatinous material, with a glistening appearance and slimy consistency, coated the inner surface of the thick wall. the cyst contained clear, viscid fluid with a s ...200818156972
centrin/cdc31 is a novel regulator of protein degradation.rad23 is required for efficient protein degradation and performs an important role in nucleotide excision repair. saccharomyces cerevisiae rad23, and its human counterpart (hhr23), are present in a complex containing the dna repair factor rad4 (termed xpc, for xeroderma pigmentosum group c, in humans). xpc/hhr23 was also reported to bind centrin-2, a member of the superfamily of calcium-binding ef-hand proteins. we report here that yeast centrin, which is encoded by cdc31, is similarly present i ...200818160718
the cytoplasmic domain of chondrolectin interacts with the beta-subunit of rab geranylgeranyl transferase.mouse chondrolectin (chodl) was isolated out of the tail tip of four-day old 129/svj mice as a by-product of a pcr-based subtractive cdna library screening. the gene is predominantly expressed in adult skeletal muscle, heart, testes and lungs and in embryonic stadia. chodl is the mouse homologue of human chondrolectin (chodl), a gene that encodes for a type ia transmembrane protein and that is expressed in human testis, prostate, heart and skeletal muscle tissue. chodl-splice variants (chodl ( f ...200818161010
a systematic single nucleotide polymorphism screen to fine-map alcohol dependence genes on chromosome 7 identifies association with a novel susceptibility gene acn9.chromosome 7 has shown consistent evidence of linkage with a variety of phenotypes related to alcohol dependence in the collaborative study on the genetics of alcoholism (coga) project. with a sample of 262 densely affected families, a peak logarithm of odds (lod) score for alcohol dependence of 2.9 was observed at d7s1799. the lod score in the region increased to 4.1 when a subset of the sample was genotyped with the illumina linkage iii panel for the genetic analysis workshop 14 (gaw14). to fo ...200818163977
identification of flotillin-1 as an interacting protein for antisecretory factor.antisecretory factor (af) also named s5a/rpn10 was originally identified through its capacity to inhibit intestinal hypersecretion and was later shown to be a component in the proteasome complex. af is also a potent anti-inflammatory agent and can act as a neuromodulator. in this study we used yeast two-hybrid screens, with yeast strain pj692a transformed with the bait vector pgbkt7 (af aa 1-105) against yeast strain y187 pretransformed with human brain or placenta cdna libraries, to identify af ...200818164080
general transcription factor iia-gamma increases osteoblast-specific osteocalcin gene expression via activating transcription factor 4 and runt-related transcription factor 2.atf4 (activating transcription factor 4) is an osteoblast-enriched transcription factor that regulates terminal osteoblast differentiation and bone formation. atf4 knock-out mice have reduced bone mass (severe osteoporosis) throughout life. runx2 (runt-related transcription factor 2) is a runt domain-containing transcription factor that is essential for bone formation during embryogenesis and postnatal life. in this study, we identified general transcription factor iia gamma (tfiia gamma) as a r ...200818171674
centrin 2 localizes to the vertebrate nuclear pore and plays a role in mrna and protein export.centrins in vertebrates have traditionally been associated with microtubule-nucleating centers such as the centrosome. unexpectedly, we found centrin 2 to associate biochemically with nucleoporins, including the xenopus laevis nup107-160 complex, a critical subunit of the vertebrate nuclear pore in interphase and of the kinetochores and spindle poles in mitosis. immunofluorescence of xenopus cells and in vitro reconstituted nuclei indeed revealed centrin 2 localized at the nuclear pores. use of ...200818172010
the cloning of dmc1 cdnas and a comparative study of its expression in different ploidy cyprinid fishes.dmc1 (disrupted meiotic cdna) is a functionally specific gene, which was firstly discovered in yeast and then found to encode a protein required for homologous chromosome synapsis during the process of meiosis. in this investigation, we cloned the partial cdnas of dmc1 of diploid red crucian carp, japanese crucian carp, common carp, triploid crucian carp and allotetraploid hybrids by using a pair of degenerate primers based on the conservative sequence of amino acids of the dmc1 protein in yeast ...200818176789
biochemical and genetic analysis of the phosphoethanolamine methyltransferase of the human malaria parasite plasmodium falciparum.the pfpmt enzyme of plasmodium falciparum, the agent of severe human malaria, is a member of a large family of known and predicted phosphoethanolamine methyltransferases (pmts) recently identified in plants, worms, and protozoa. functional studies in p. falciparum revealed that pfpmt plays a critical role in the synthesis of phosphatidylcholine via a plant-like pathway involving serine decarboxylation and phosphoethanolamine methylation. despite their important biological functions, pmt structur ...200818178564
akip1 enhances nf-kappab-dependent gene expression by promoting the nuclear retention and phosphorylation of p65.in this study, we have identified protein kinase a-interacting protein 1 (akip1) as a binding partner of nf-kappab p65 subunit, and akip1 enhances the nf-kappab-mediated gene expression. akip1 is a nuclear protein and known to interact with the catalytic subunit of pka (pkac). we identified akip1 by a yeast two-hybrid screen using the n terminus region of p65 as bait. the interaction between akip1 and p65 was confirmed by glutathione s-transferase pull-down assay in vitro and immunoprecipitation ...200818178962
complementary use of molecular and element-specific mass spectrometry for identification of selenium compounds related to human selenium metabolism.the aim of this paper is to give an overview of analytical data on the identification of selenium compounds in biological samples with relevance for selenium metabolism. only studies applying the combination of element-specific inductively coupled plasma mass spectrometry as well as molecular electrospray mass spectrometry detection have been included. hence, selenium compounds are only considered identified if molecular mass spectra obtained by analysis of the authentic biological sample have b ...200818180909
sirt1 acts as a nutrient-sensitive growth suppressor and its loss is associated with increased ampk and telomerase activity.sirt1, the mammalian homolog of sir2 in saccharomyces cerevisiae, is an nad-dependent deacetylase implicated in regulation of lifespan. by designing effective short hairpin rnas and a silent shrna-resistant mutant sirt1 in a genetically defined system, we show that efficient inhibition of sirt1 in telomerase-immortalized human cells enhanced cell growth under normal and nutrient limiting conditions. hematopoietic stem cells obtained from sirt1-deficient mice also showed increased growth capacity ...200818184747
the neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury.epithelia establish a microbial barrier against infection through the production of antimicrobial peptides (amps). in this study, we investigated whether catestatin (cst), a peptide derived from the neuroendocrine protein chromogranin a (chga), is a functional amp and is present in the epidermis. we show that cst is antimicrobial against relevant skin microbes, including gram-positive and gram-negative bacteria, yeast, and fungi. the antimicrobial mechanism of cst was found to be similar to othe ...200818185531
protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains.protein phosphatase 6 (pp6) is an essential ser/thr phosphatase conserved among eukaryotes. the saccharomyces cerevisiae homologue of pp6 called sit4 depends on association with saps domain subunits. this study used a human saps domain subunit flag-pp6r1 to identify endogenous interacting proteins. mass spectrometry identified coprecipitating proteins as pp6 catalytic subunit and three ankyrin repeat proteins (ankrd28, ankrd44, and ankrd52). these proteins have extensive sequence identity to one ...200818186651
hydrogen peroxide-induced gene expression across kingdoms: a comparative analysis.cells react to oxidative stress conditions by launching a defense response through the induction of nuclear gene expression. the advent of microarray technologies allowed monitoring of oxidative stress-dependent changes of transcript levels at a comprehensive and genome-wide scale, resulting in a series of inventories of differentially expressed genes in different organisms. we performed a meta-analysis on hydrogen peroxide (h(2)o(2))-induced gene expression in the cyanobacterium synechocystis p ...200818187560
analysis of udp-galactose 4'-epimerase mutations associated with the intermediate form of type iii galactosaemia.type iii galactosaemia is a hereditary disease caused by reduced activity in the leloir pathway enzyme, udp-galactose 4'-epimerase (gale). traditionally, the condition has been divided into two forms-a mild, or peripheral, form and a severe, or generalized, form. recently it has become apparent that there are disease states which are intermediate between these two extremes. three mutations associated with this intermediate form (s81r, t150m and p293l) were analysed for their kinetic and structur ...200818188677
mapping of protein-protein interaction sites by the 'absence of interference' approach.protein-protein interactions are critical to most biological processes, and locating protein-protein interfaces on protein structures is an important task in molecular biology. we developed a new experimental strategy called the 'absence of interference' approach to determine surface residues involved in protein-protein interaction of established yeast two-hybrid pairs of interacting proteins. one of the proteins is subjected to high-level randomization by error-prone pcr. the resulting library ...200818191145
dynamic covariation between gene expression and genome characteristics.gene and protein expression is controlled so that cells can react to changing intra- and extracellular signals by modulating biochemical networks and pathways. we have previously shown that gene expression and the properties of expressed proteins are dynamically correlated. here we investigated correlations between gene related parameters and gene expression patterns, and found statistically significant correlations in microarray datasets for different cell types, organisms and processes, includ ...200818191345
hbv x protein targets hbubr1, which induces dysregulation of the mitotic checkpoint.accurate chromosomal segregation is monitored by the mitotic checkpoint, and an increased rate of chromosomal missegregation leads to chromosomal instability (cin). here, we demonstrate that the hbv x protein (hbx) binds bubr1, a component of the mitotic checkpoint complex and co-localizes with bubr1 at the kinetochores. hbx binding to bubr1 attenuates the association between bubr1 and cdc20, an activator of the anaphase-promoting complex/cyclosome (apc/c) and induces slippage of mitotic arrest ...200818193091
slic-1/sorting nexin 20: a novel sorting nexin that directs subcellular distribution of psgl-1.p-selectin glycoprotein ligand-1 (psgl-1) is a mucin-like glycoprotein expressed on the surface of leukocytes that serves as the major ligand for the selectin family of adhesion molecules and functions in leukocyte tethering and rolling on activated endothelium and platelets. previous studies have implicated the highly conserved cytoplasmic domain of psgl-1 in regulating outside-in signaling of integrin activation. however, molecules that physically and functionally interact with this domain are ...200818196517
a comparative pharmacokinetic study of recombinant human serum albumin with plasma-derived human serum albumin in patients with liver cirrhosis.we conducted an open-label, parallel-group study of the high purity, mass-produced recombinant human serum albumin (rhsa), derived from the methylotrophic yeast pichia pastoris, to compare pharmacokinetics and ensure bioequivalence with plasma-derived human serum albumin (phsa) in 22 patients with liver cirrhosis. both rhsa and phsa groups enrolled 11 patients each, assigned according to predose serum albumin concentrations using the minimization method. pharmacokinetic and safety profiles for 3 ...200818199895
detection and identification of plasma proteins that bind glialcam using proteinchip arrays, seldi-tof ms, and nano-lc ms/ms.in order to fully understand biological processes it is essential to identify interactions in protein complexes. there are several techniques available to study this type of interactions, such as yeast two-hybrid screens, affinity chromatography, and coimmunoprecipitation. we propose a novel strategy to identify protein-protein interactions, comprised of first detecting the interactions using proteinchips and seldi-tof ms, followed by the isolation of the interacting proteins through affinity be ...200818203261
natural and recombinant human glycodelin activate a proapoptotic gene cascade in monocyte cells.glycodelin-a (gda) is a member of the superfamily of lipocalins and the predominant glycoprotein secreted by human and primate endometrium in the secretory and early pregnancy phases. gda can inhibit nk cell activity, t cell proliferation, and chemotaxis of monocytes. its physiological function is thought to mediate immunotolerance at the fetomaternal interface. in the present studies, we engineered recombinant gd (rgd) in yeast and tested its biological effects on monocyte viability. rgd, like ...200818203874
identification of small molecules inducing apoptosis by cell-based assay using fission yeast deletion mutants.the cell-based assay using yeast deletion mutants has been recognized as an efficient analysis to discover therapeutic compounds and reveal their mode of action. in this study, s. pombe deletion mutants-based hts screening was carried out to identify potential anti-cancer agents. the nci chemical library of 5700 compounds was screened using kit strains, which consisted of s. pombe mutants harboring deletions in genes involved in dna repair and mitotic control. during the screening, we identified ...200818204818
direct visualization of asymmetric adenine-nucleotide-induced conformational changes in mutl alpha.mutl alpha, the heterodimeric eukaryotic mutl homolog, is required for dna mismatch repair (mmr) in vivo. it has been suggested that conformational changes, modulated by adenine nucleotides, mediate the interactions of mutl alpha with other proteins in the mmr pathway, coordinating the recognition of dna mismatches by muts alpha and the activation of mutl alpha with the downstream events that lead to repair. thus far, the only evidence for these conformational changes has come from x-ray crystal ...200818206974
alterations of brms1-arid4a interaction modify gene expression but still suppress metastasis in human breast cancer cells.the brms1 metastasis suppressor interacts with the protein at-rich interactive domain 4a (arid4a, rbbp1) as part of sin3.histone deacetylase chromatin remodeling complexes. these transcriptional co-repressors regulate diverse cell phenotypes depending upon complex composition. to define brms1 complexes and their roles in metastasis suppression, we generated brms1 mutants (brms1(mut)) and mapped arid4a interactions. brms1(l174d) disrupted direct interaction with arid4a in yeast two-hybrid genetic ...200818211900
ubiquitin binding mediates the nf-kappab inhibitory potential of abin proteins.deregulated nuclear factor kappab (nf-kappab) activation plays an important role in inflammation and tumorigenesis. abin proteins have been characterized as negative regulators of nf-kappab signaling. however, their mechanism of nf-kappab inhibition remained unclear. with the help of a yeast two-hybrid screen, we identified abin proteins as novel ubiquitin-interacting proteins. the minimal ubiquitin-binding domain (ubd) corresponds to the abin homology domain 2 (ahd2) and is highly conserved in ...200818212736
fancg promotes formation of a newly identified protein complex containing brca2, fancd2 and xrcc3.fanconi anemia (fa) is a human disorder characterized by cancer susceptibility and cellular sensitivity to dna crosslinks and other damages. thirteen complementation groups and genes are identified, including brca2, which is defective in the fa-d1 group. eight of the fa proteins, including fancg, participate in a nuclear core complex that is required for the monoubiquitylation of fancd2 and fanci. fancd2, like fancd1/brca2, is not part of the core complex, and we previously showed direct brca2-f ...200818212739
proteasome-dependent degradation of alpha-catenin is regulated by interaction with armc8alpha.armc8 (armadillo-repeat-containing protein 8) is a key component of the ctlh (c-terminal to lissencephaly type-1-like homology motif) complex in mammalian cells. this complex is well conserved in saccharomyces cerevisiae and has been characterized as a fbpase (fructose-1, 6-bisphosphatase)-degrading complex. the yeast homologue of armc8, gid (glucose-induced degradation) 5p, plays an essential role in the ubiquitin- and proteasome-dependent degradation of fbpase. to elucidate the function of arm ...200818215130
tor regulation of agc kinases in yeast and mammals.the tor (target of rapamycin), an atypical protein kinase, is evolutionarily conserved from yeast to man. pharmacological studies using rapamycin to inhibit tor and yeast genetic studies have provided key insights on the function of tor in growth regulation. one of the first bona fide cellular targets of tor was the mammalian protein kinase p70 s6k (p70 s6 kinase), a member of a family of kinases called agc (protein kinase a/protein kinase g/protein kinase c-family) kinases, which include pka (c ...200818215152
jab1 accelerates mitochondrial apoptosis by interaction with proapoptotic bclgs.the bcl-2 family of proteins is the key regulators of cell apoptosis at the mitochondria level. the bh3-only pro-apoptotic member bclgs was unique among the family due to its highly specific expression in human testis and has been demonstrated to induce apoptosis dependent on the bh3 domain. however, the molecular mechanism of bclgs-induced apoptosis remains unclear. here we show that overexpression of bclgs could induce bax expression upregulation and translocation to mitochondria, cytochrome c ...200818006276
ultra short yeast tropomyosins show novel myosin regulation.tropomyosin (tm) is an alpha-helical coiled-coil actin-binding protein present in all eukaryotes from yeast to man. its functional role has been best described in muscle regulation; however its much wider role in cytoskeletal actin regulation is still to be clarified. isoforms vary in size from 284 or 248 amino acids in vertebrates, to 199 and 161 amino acids in yeast, spanning from 7 to 4 actin binding sites respectively. in saccharomyces cerevisiae, the larger ytm1 protein is produced by an in ...200818006493
knockdown of human mcm10 activates g2 checkpoint pathway.mcm10 has been shown to be a component for the elongation step of chromosome replication in model organisms such as yeast. in the accompanying manuscript [j.h. park, s.w. bang, y. jeon, s. kang, d.s. hwang, knockdown of human mcm10 exhibits delayed and incomplete chromosome replication, biochem. biophys. res. commun. (2007) 365 (2008) 575-582.], we reported that knockdown of human mcm10 protein exhibits delayed and incomplete chromosomal dna replication. in this report, we examined the consequen ...200817997981
over-expression of the catalytic core of mitochondrial dna (mtdna) polymerase in the nervous system of drosophila melanogaster reduces median life span by inducing mtdna depletion.dna polymerase gamma (pol gamma) is the sole dna polymerase devoted to mitochondrial dna (mtdna) replication. we have characterized the molecular and physiological effects of over-expression of the catalytic subunit of pol gamma, pol gamma-alpha, in the nervous system of drosophila melanogaster using the upstream activation sequence (uas)/yeast transcriptional activator by binding to uas (gal4) system. tissue-specific over-expression of pol gamma-alpha was confirmed by immunoblot analysis, where ...200817999718
modified vaccinia virus ankara as a vector for suicide gene therapy.modified vaccinia virus ankara (mva) has been used successfully to express various antigens for the development of vaccines. here we show that mva can also be used as an efficient vector for the transfer of suicide genes to cancer cells. we have generated a new and highly potent suicide gene, fcu1, which encodes a fusion protein derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. we now describe the therapeutic benefit of using mva to deliver and express the fcu ...200817992203
subversion of cellular autophagy by anaplasma phagocytophilum.anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligatory intracellular pathogen. after entry into host cells, the bacterium is diverted from the endosomal pathway and replicates in a membrane-bound compartment devoid of endosomal or lysosomal markers. here, we show that several hallmarks of early autophagosomes can be identified in a. phagocytophilum replicative inclusions, including a double-lipid bilayer membrane and colocalization with gfp-tagged lc3 ...200817979984
human antibody libraries: a race to engineer and explore a larger diversity.several recombinant antibody libraries associated with different screening technologies have been generated since the first steps of antibody engineering 15 years ago, in order to isolate human monoclonal antibodies. in this race to isolate antibody with virtually any specificity, innovative strategies have been developed to clone natural antibody repertoires or to increase library diversity beyond the scope of the immune system. after the in vitro transfer of the natural diversity, the second g ...200817981617
humanization of antibodies.humanization has played a fundamental role in the remarkable progress of antibodies as therapeutic reagents. here we have reviewed the publications on antibody humanization since the first report on cdr grafting in the second half of the 1980's up to june 2007. we describe the two main trends in the field: rational and empirical methods to humanize antibodies. rational methods rely on the so-called design cycle. it consists of generating a small set of variants, which are designed based on the a ...200817981654
chromosome instability in yeast and its implications to the study of human cancer.one of the most important events during cell division is chromosome segregation, which allows that each daughter cell receives one set of duplicated chromosomes. any mistakes in chromosome segregation process will result in loss or gain of chromosomes after mitosis, which may lead to either down-regulation of cancer suppressors or up-regulation of oncogenes. therefore, defects in chromosome segregation may contribute to cancer development. as chromosome segregation is a conserved cellular proces ...200817981694
upgrades to stellabase facilitate medical and genetic studies on the starlet sea anemone, nematostella vectensis.the starlet sea anemone, nematostella vectensis, is a basal metazoan organism that has recently emerged as an important model system in developmental biology and evolutionary genomics. stellabase, the nematostella genomics database (http://stellabase.org), was developed in 2005 as a resource to support the nematostella research community. recently, it has become apparent that nematostella may be a particularly useful system for studying (i) microevolutionary variation in natural populations, and ...200817982171
protective up-regulation of ck2 by mutant huntingtin in cells co-expressing nmda receptors.huntington's disease is caused by a polyglutamine expansion in the huntingtin (htt) protein, and previous data indicate that over-activation of nmda receptors (nmdars) may be involved in the selective degeneration of cells expressing nr1/nr2b nmdars. we used kinetworkstrade mark multi-immunoblotting screens to examine expression of 76 protein kinases, 18 protein phosphatases, 25 heat shock/stress proteins, and 27 apoptosis proteins in human embryonic kidney 293 cells transfected with nr1/nr2b an ...200817971125
phosphorylation-dependent binding of cyclin b1 to a cdc6-like domain of human separase.sister chromatids are held together by the ring-shaped cohesin complex, which likely entraps both dna-double strands in its middle. this tie is resolved in anaphase when separase, a giant protease, becomes active and cleaves the kleisin subunit of cohesin. premature activation of separase and, hence, chromosome missegregation are prevented by at least two inhibitory mechanisms. although securin has long been appreciated as a direct inhibitor of separase, surprisingly its loss has basically no ph ...200817974570
hccrbp-1 directly interacting with hccr-1 induces tumorigenesis through p53 stabilization.oncogene hccr-1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. hccr transgenic mice developed breast cancers but it is unknown how hccr-1 contributes to human tumorigenesis. this study identified a hccr-1-binding protein 1 (hccrbp-1) as an hccr binding partner by performing yeast two hybrid screening. their endogenous interaction was further confirmed by coimmunoprecipitation experiments. these two proteins colocalized in the mitochondria. ...200817943721
a new highly androgen specific yeast biosensor, enabling optimisation of (q)sar model approaches.recently we constructed recombinant yeast cells that express the human androgen receptor (har) and yeast enhanced green fluorescent protein (yegfp), the latter in response to androgens. when exposed to 17beta-testosterone, the concentration where half-maximal activation is reached (ec50) was 50 nm. relative androgenic potencies (rap), defined as the ratio between the ec50 of 17beta-testosterone and the ec50 of the compound, were 1.7, 1.2 and 0.008 for 19-nortestosterone, tetrahydrogestrinone and ...200817945480
phylomedb: a database for genome-wide collections of gene phylogenies.the complete collection of evolutionary histories of all genes in a genome, also known as phylome, constitutes a valuable source of information. the reconstruction of phylomes has been previously prevented by large demands of time and computer power, but is now feasible thanks to recent developments in computers and algorithms. to provide a publicly available repository of complete phylomes that allows researchers to access and store large-scale phylogenomic analyses, we have developed phylomedb ...200817962297
cholestin (monascus purpureus rice) inhibits homocysteine-induced reactive oxygen species generation, nuclear factor-kappab activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial cells.hyperhomocysteinemia is associated with dysfunction and an independent risk factor of cardiovascular diseases. cholestin (monascus purpureus-fermented rice), contains a naturally-occurring statin, which has lipid-modulating and anti-inflammatory effects. we investigated the effects of cholestin extract on the expression of vascular cell adhesion molecule-1 (vcam-1) by homocysteine (hcy)-treated human aortic endothelial cells (haecs). supplement of haecs with cholestin extract significantly suppr ...200817906965
ecm11 protein of yeast saccharomyces cerevisiae is regulated by sumoylation during meiosis.damaged regulation of the small ubiquitin-like modifier (sumo) system contributes to some human diseases; therefore, it is very important to identify the sumo targets and to determine the function of their sumoylation. in this study, it is shown that ecm11 protein in saccharomyces cerevisiae is modified by sumo during meiosis. it is known that ecm11 is required in the early stages of yeast meiosis where its function is related to dna replication and crossing over. here it is shown that the level ...200817888002
letm1, deleted in wolf-hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability.wolf-hirschhorn syndrome (whs) is a complex congenital syndrome caused by a monoallelic deletion of the short arm of chromosome 4. seizures in whs have been associated with deletion of letm1 gene. letm1 encodes for the human homologue of yeast mdm38p, a mitochondria-shaping protein of unclear function. here we show that human letm1 is located in the inner membrane, exposed to the matrix and oligomerized in higher molecular weight complexes of unknown composition. down-regulation of letm1 did not ...200817925330
high-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias.fatty acids are implicated in the development of dyslipidemias, leading to type 2 diabetes and cardiovascular disease. we used a standardized small compound library to screen humanized yeast to identify compounds that inhibit fatty acid transport protein (fatp)-mediated fatty acid uptake into cells. this screening procedure used live yeast cells expressing human fatp2 to identify small compounds that reduced the import of a fluorescent fatty acid analog, 4,4-difluoro-5-methyl-4-bora-3a,4a-diaza- ...200817928635
many microbe microarrays database: uniformly normalized affymetrix compendia with structured experimental metadata.many microbe microarrays database (m3d) is designed to facilitate the analysis and visualization of expression data in compendia compiled from multiple laboratories. m3d contains over a thousand affymetrix microarrays for escherichia coli, saccharomyces cerevisiae and shewanella oneidensis. the expression data is uniformly normalized to make the data generated by different laboratories and researchers more comparable. to facilitate computational analyses, m3d provides raw data (cel file) and nor ...200817932051
androgen receptor transactivation assay using green fluorescent protein as a reporter.for screening of a large number of samples for androgenic activity, a robust system with minimal handling is required. the coding sequence for human androgen receptor (ar) was inserted into expression plasmid yepbubi-flag1, resulting in the plasmid yepbubiflag-ar, and the estrogen response element (ere) on the reporter vector yrpe2 was replaced by an androgen response element (are), resulting in the plasmid yrpe2-are. thus, a fully functional transactivation assay system with beta-galactosidase ...200817935685
emerging roles of the oxysterol-binding protein family in metabolism, transport, and signaling.osbp (oxysterol-binding protein) and orps (osbp-related proteins) constitute an enigmatic eukaryotic protein family that is united by a signature domain that binds oxysterols, sterols, and possibly other hydrophobic ligands. the human genome contains 12 osbp/orp family members genes, while that of the budding yeast saccharomyces cerevisiae encodes seven osbp homologues (osh). of these, osh4 (also referred to as kes1) has been the most widely studied to date. recently, three-dimensional crystal s ...200817938859
molecular cloning and responsive expression to injury stimulus of a defender against cell death 1 (dad1) gene from bay scallops argopecten irradians.apoptosis is an active process of cell death, which is an integral part of growth and development in multicellular organisms. the defender against cell death 1 (dad1), the regulatory protein to inhibit the apoptosis process, was first cloned from the bay scallop argopecten irradians by randomly sequencing a whole tissue cdna library and rapid amplification of cdna end (race). the full-length cdna of the a. irradians dad1 was 607 bp, consist of a 5'-terminal untranslated region (utr) of 63 bp, a ...200817294251
a proteomic view of candida albicans yeast cell metabolism in exponential and stationary growth phases.the facultative pathogenic fungus candida albicans has to come up with dynamic metabolic adaptation programs in order to be able to survive within a variety of niches in the human host, each of which has its different nutrient availability. using a large-scale two-dimensional (2-d) protein gel electrophoresis approach, we analyzed the adaptation mechanisms to nutrient limitation in a batch culture in complex medium with glucose as carbon source. to this end, we constructed a 2-d reference map of ...200817588813
the c terminus of the synovial sarcoma-associated ssx proteins interacts with the lim homeobox protein lhx4.as a result of the synovial sarcoma-associated t(x;18) translocation, the ss18 gene on chromosome 18 is fused to either one of the three closely related ssx genes on the x chromosome. the ss18 protein is thought to act as a transcriptional co-activator, whereas the ssx proteins are thought to act as transcriptional corepressors. the main ssx-repression domain is located in its c terminus, a domain that is retained in the respective ss18-ssx fusion proteins. both the ss18 and ssx proteins lack dn ...200817667940
endocrine modulation and toxic effects of two commonly used uv screens on the aquatic invertebrates potamopyrgus antipodarum and lumbriculus variegatus.the two uv screens 3-benzylidene-camphor (3-bc) and 3-(4'-methylbenzylidene)-camphor (4-mbc) were tested regarding their toxicity and estrogenic activity. the yeast estrogen screen (yes) and two sediment assays with the freshwater invertebrates lumbriculus variegatus and potamopyrgus antipodarum were performed. in the yes, both substances activated the human estrogen receptor alpha with ec50 values of 44.2 microm for 3-bc and 44.3 microm for 4-mbc, whereby 4-mbc attained only 8% of the maximal r ...200817669564
the association between rad18 arg302gln polymorphism and the risk of human non-small-cell lung cancer.the repair enzyme rad18 plays a key role in the post-replication repair process in various organisms from yeast to human, and the molecular function of the rad18 protein has been elucidated. single nucleotide polymorphism (snp) of arginine (arg, cga) or glutamine (gln, caa) at codon 302 is known on rad18; however, the association between the snp and the risk of any human cancers including non-small-cell lung cancer (nsclc) has not been reported. we therefore investigated the relationship between ...200817624554
analysis of transactivation capability and conformation of p53 temperature-dependent mutants and their reactivation by amifostine in yeast.the p53 gene is often mutated during cancer development. frequency and functional consequences of these mutations vary in different tumor types. we analysed conformation and temperature dependency of 23 partially inactivating temperature-dependent (td) p53 mutants derived from various human tumors in yeast. we found considerable differences in transactivation capabilities and discriminative character of various p53 mutants. no correlations in transactivation rates and conformations of the td p53 ...200817724467
molecular characterisation of a second structurally unusual ar-smad without an mh1 domain and a smad4 orthologue from echinococcus multilocularis.members of the transforming growth factor-beta/bone morphogenetic protein (tgf-beta/bmp) family of cytokines play crucial roles in animal development and are candidate molecules for host-parasite cross-communication in helminth diseases. tgf-beta/bmp-signalling involves binding of the cytokines to receptor kinases which subsequently activate intracellular transcription factors of the smad family. we have previously characterized two members of the receptor-regulated smad (r-smad) family, emsmada ...200817845804
[cryptococcus neoformans meningitis in a hiv negative miliary tuberculosis-suspected patient].cryptococcosis caused by cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. it is more common among immunosupressed patients such as human immunodeficiency virus (hiv) positive ones. in this report we present a case with c. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without hiv infection. a-70-years-old m ...200818822899
recruitment of saccharomyces cerevisiae dnl4-lif1 complex to a double-strand break requires interactions with yku80 and the xrs2 fha domain.nonhomologous end joining (nhej) in yeast depends on eight different proteins in at least three different functional complexes: yku70-yku80 (ku), dnl4-lif1-nej1 (dna ligase iv), and mre11-rad50-xrs2 (mrx). interactions between these complexes at dna double-strand breaks (dsbs) are poorly understood but critical for the completion of repair. we previously identified two such contacts that are redundantly required for nhej, one between dnl4 and the c terminus of yku80 and one between the forkhead- ...200818832348
impaired dna damage response, genome instability, and tumorigenesis in sirt1 mutant mice.in lower eukaryotes, sir2 serves as a histone deacetylase and is implicated in chromatin silencing, longevity, and genome stability. here we mutated the sirt1 gene, a homolog of yeast sir2, in mice to study its function. we show that a majority of sirt1 null embryos die between e9.5 and e14.5, displaying altered histone modification, impaired dna damage response, and reduced ability to repair dna damage. we demonstrate that sirt1(+/-);p53(+/-) mice develop tumors in multiple tissues, whereas act ...200818835033
sod1, a new kluyveromyces lactis helper gene for heterologous protein secretion.bottlenecks in protein expression and secretion often limit the development of industrial processes. by manipulating chaperone and foldase levels, improvements in yeast secretion were found for a number of proteins. recently, sustained endoplasmic reticulum stress, occurring due to recombinant protein production, was reported to cause oxidative stress in yeast. saccharomyces cerevisiae cells are able to trigger an adaptive response to oxidative-stress conditions, resulting in the upregulation of ...200818836000
[high level expression, purification and characterization of human kallikrein-1 in pichia pastoris].human kallikrein-1 (hk1) gene was cloned from kidney tissues cdna, it was inserted into the plasmid ppiczalphaa, then the yeast expression vector ppiczalpha-hk1 was constructed. after transformed into pichia pastoris host x33, high-level expression transformants were screened by escalating the concentration of zeocin (from 500 to 700 microg/ml) of ypd plate and medium. when temperature was 30 degrees c, ph 6.0 with induction duration of 64 hours in the 30 l fermenter, the highest yield can reach ...200818837393
'knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies.recent significant advances in molecular biology have generated genetically modified bacteria, yeast, nematodes, fruit flies, and fish. however, it is the genetic modification of mammalian model organisms, particularly the mouse, that has the greatest potential to shed light on human development, physiology and pathology in ways that have significant implications for neonatal and paediatric clinical practice. here, we review some of the techniques for knocking out (inactivating), mutating and kn ...200818838236
human atac is a gcn5/pcaf-containing acetylase complex with a novel nc2-like histone fold module that interacts with the tata-binding protein.eukaryotic gcn5 acetyltransferases influence diverse biological processes by acetylating histones and non-histone proteins and regulating chromatin and gene-specific transcription as part of multiprotein complexes. in lower eukaryotes and invertebrates, these complexes include the yeast ada complex that is still incompletely understood; the saga (spt-ada-gcn5 acetylase) complexes from yeast to drosophila that are mostly coactivators; and the atac (ada two-a containing) complex, only known in dro ...200818838386
hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of cdc37.activation of protein kinase clients by the hsp90 system is mediated by the cochaperone protein cdc37. cdc37 requires phosphorylation at ser13, but little is known about the regulation of this essential posttranslational modification. we show that ser13 of uncomplexed cdc37 is phosphorylated in vivo, as well as in binary complex with a kinase (c-k), or in ternary complex with hsp90 and kinase (h-c-k). whereas pser13-cdc37 in the h-c-k complex is resistant to nonspecific phosphatases, it is effic ...200818922470
distinct modes of regulation of the uch37 deubiquitinating enzyme in the proteasome and in the ino80 chromatin-remodeling complex.deubiquitinating enzymes (dubs) are proteases that can antagonize ubiquitin-mediated signaling by disassembling ubiquitin-protein conjugates. how dubs are regulated in vivo and how their substrate specificities are achieved are largely unknown. the conserved dub uch37 is found on proteasomes in organisms ranging from fission yeast to humans. deubiquitination by uch37 is activated by proteasomal binding, which enables uch37 to process polyubiquitin chains. here we show that in the nucleus uch37 i ...200818922472
molecular analysis of the penicillium marneffei glyceraldehyde-3-phosphate dehydrogenase-encoding gene (gpda) and differential expression of gpda and the isocitrate lyase-encoding gene (acud) upon internalization by murine macrophages.penicillium marneffei is an intracellular dimorphic fungus that can cause a fatal disseminated disease in human immunodeficiency virus-infected patients. the factors that affect the pathogenicity of this fungus remain unclear. here, we report the isolation and characterization of the gpda cdna and genomic clones encoding glyceraldehyde-3-phosphate dehydrogenase (gapdh) in p. marneffei. phylogenetic analysis of gapdh amino acid sequences demonstrated the evolutionary relationship of p. marneffei ...200818927407
mink is a rap2 effector for phosphorylation of the postsynaptic scaffold protein tanc1.rap1 and rap2 are similar ras-like g proteins but perform distinct functions. by the affinity chromatography/mass-spectrometry approach and the yeast two-hybrid screening, we identified misshapen/niks-related kinase (mink) as a novel rap2-interacting protein that does not interact with rap1 or ras. mink is a member of the ste20 group of mitogen-activated protein kinase kinase kinase kinases. the interaction between mink and rap2 was gtp-dependent and required phe39 within the effector region of ...200818930710
human metapneumovirus nucleoprotein and phosphoprotein interact and provide the minimal requirements for inclusion body formation.human metapneumovirus (hmpv) is a recently discovered paramyxovirus of the subfamily pneumovirinae, which also includes avian pneumovirus and human respiratory syncytial virus (hrsv). hmpv is an important cause of respiratory disease worldwide. to understand early events in hmpv replication, cdnas encoding the hmpv nucleoprotein (n), phosphoprotein (p), matrix protein (m), m2-1 protein and m2-2 protein were cloned from cells infected with the genotype a1 hmpv wild-type strain tn/96-12. hmpv n an ...200818931065
a tropomyosin 1 induced defect in cytokinesis can be rescued by elevated expression of cofilin.cytokinesis in eukaryotic cells is mediated by the contractile ring, an actomyosin-based structure which provides the force required to separate daughter cells. isoforms of the actin-binding protein tropomyosin are also localised to the contractile ring in both fission yeast and human astrocytes. although tropomyosin is required for cytokinesis in yeast, its precise role in the contractile ring is unknown. in this study we find that increased expression of a single tropomyosin isoform, tropomyos ...200818937355
architecture of the pontin/reptin complex, essential in the assembly of several macromolecular complexes.pontin and reptin belong to the aaa+ family, and they are essential for the structural integrity and catalytic activity of several chromatin remodeling complexes. they are also indispensable for the assembly of several ribonucleoprotein complexes, including telomerase. here, we propose a structural model of the yeast pontin/reptin complex based on a cryo-electron microscopy reconstruction at 13 a. pontin/reptin hetero-dodecamers were purified from in vivo assembled complexes forming a double rin ...200818940606
c/ebp homology protein (chop) interacts with activating transcription factor 4 (atf4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene.c/ebp homology protein (chop), a stress-induced transcription factor, is involved in transcriptional regulation, cell cycle, and apoptosis. the present studies identified chop as an interacting partner of activating transcription factor (atf) 4 in a yeast two-hybrid screen and confirmed their interaction in hek293t cells. chop protein levels rose modestly and transiently during amino acid deprivation, whereas endoplasmic reticulum stress caused a much higher and sustained expression of chop prot ...200818940792
instability of superoxide dismutase 1 of drosophila in mutants deficient for its cognate copper chaperone.copper,zinc superoxide dismutase (sod1) in mammals is activated principally via a copper chaperone (ccs) and to a lesser degree by a ccs-independent pathway of unknown nature. in this study, we have characterized the requirement for ccs in activating sod1 from drosophila. a ccs-null mutant (ccs(n)(29)(e)) of drosophila was created and found to phenotypically resemble drosophila sod1-null mutants in terms of reduced adult life span, hypersensitivity to oxidative stress, and loss of cytosolic acon ...200818948262
kinase requirements in human cells: ii. genetic interaction screens identify kinase requirements following hpv16 e7 expression in cancer cells.human papillomavirus (hpv) oncoproteins subvert cellular signaling pathways, including kinase pathways, during the carcinogenic process. to identify kinases targeted by the hpv16 e7 oncoprotein, shrna kinase screens were performed in rko colorectal carcinoma cell lines that differ only in their expression of hpv16 e7. our screens identified kinases that were essential for the survival of rko cells, but not essential for rko cells expressing hpv16 e7. these kinases include cdk6, erbb3, fyn, aak1, ...200818948598
Displaying items 7501 - 7600 of 8978