| 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 ... | 2008 | 18930710 |
| expression cloning of tmem16a as a calcium-activated chloride channel subunit. | calcium-activated chloride channels (caccs) are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction. other crucial roles of caccs include action potential generation in characean algae and prevention of polyspermia in frog egg membrane. none of the known molecular candidates share properties characteristic of most caccs in native cells. using axolotl oocytes as an expression system, we have identified tmem16a as the xenopus oocyte cacc. the tmem16 family ... | 2008 | 18805094 |
| ubc9-mediated sumoylation leads to transcriptional repression of irf-1. | to characterize the regulatory mechanism of the interferon regulatory factor (irf) family, we performed yeast two-hybrid screening with irf-2 and isolated the small ubiquitin-related modifier (sumo)-conjugating enzyme ubc9, which also interacts with other irf family members irf-1 and icsbp. subsequent assays indicated that among the irf family members, only irf-1 interacts with sumo-1 through its transcriptional activation domain. the interaction between irf-1 and sumo-1 was confirmed in vitro b ... | 2008 | 18955028 |
| sequence space coverage, entropy of genomes and the potential to detect non-human dna in human samples. | genomes store information for building and maintaining organisms. complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. | 2008 | 18973670 |
| predicting protein post-translational modifications using meta-analysis of proteome scale data sets. | protein post-translational modifications are an important biological regulatory mechanism, and the rate of their discovery using high throughput techniques is rapidly increasingly. to make use of this wealth of sequence data, we introduce a new general strategy designed to predict a variety of post-translational modifications in several organisms. we used the motif-x program to determine phosphorylation motifs in yeast, fly, mouse, and man and lysine acetylation motifs in man. these motifs were ... | 2009 | 18974045 |
| intrinsic capability of budding yeast cofilin to promote turnover of tropomyosin-bound actin filaments. | the ability of actin filaments to function in cell morphogenesis and motility is closely coupled to their dynamic properties. yeast cells contain two prominent actin structures, cables and patches, both of which are rapidly assembled and disassembled. although genetic studies have shown that rapid actin turnover in patches and cables depends on cofilin, how cofilin might control cable disassembly remains unclear, because tropomyosin, a component of actin cables, is thought to protect actin filam ... | 2008 | 18982060 |
| 80k-h interacts with inositol 1,4,5-trisphosphate (ip3) receptors and regulates ip3-induced calcium release activity. | inositol 1,4,5-trisphosphate receptors (ip3rs) are intracellular channel proteins that mediate calcium (ca2+) release from the endoplasmic reticulum, and they are involved in many biological processes (e.g. fertilization, secretion, and synaptic plasticity). recent reports show that ip3r activity is strictly regulated by several interacting molecules (e.g. ip3r binding protein released with inositol 1,4,5-trisphosphate, huntingtin, presenilin, danger, and cytochrome c), and perturbation of this ... | 2009 | 18990696 |
| structural and functional differences between krit1a and krit1b isoforms: a framework for understanding ccm pathogenesis. | krit1 is a disease gene responsible for cerebral cavernous malformations (ccm). it encodes for a protein containing distinct protein-protein interaction domains, including three npxy/f motifs and a ferm domain. previously, we isolated krit1b, an isoform characterized by the alternative splicing of the 15th coding exon and suspected to cause ccm when abnormally expressed. combining homology modeling and docking methods of protein-structure and ligand binding prediction with the yeast two-hybrid a ... | 2009 | 18992740 |
| '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 ... | 2008 | 18838236 |
| restoration of electron transport without proton pumping in mammalian mitochondria. | we have restored the coq oxidative capacity of mouse mtdna-less cells (rho degrees cells) by transforming them with the alternative oxidase aox of emericella nidulans. cotransforming rho degrees cells with the nadh dehydrogenase of saccharomyces cerevisiae, ndi1 and aox recovered the nadh dh/coq reductase and the coq oxidase activities. coq oxidation by aox reduces the dependence of rho degrees cells on pyruvate and uridine. coexpression of aox and ndi1 further improves the recycling of nad(+). ... | 2008 | 19020091 |
| pcna interacts with prox1 and represses its transcriptional activity. | prox1 is a transcription factor which can function either as a transcriptional activator, transcriptional repressor or a transcriptional corepressor. this paper seeks to better understand the role of protein-protein interactions in this multitude of functions. | 2008 | 19023449 |
| activation of protein kinase czeta increases oat1 (slc22a6)- and oat3 (slc22a8)-mediated transport. | organic anion transporters (oats) play a pivotal role in the clearance of small organic anions by the kidney, yet little is known about how their activity is regulated. a yeast two-hybrid assay was used to identify putative oat3-associated proteins in the kidney. atypical protein kinase czeta (pkczeta) was shown to bind to oat3. binding was confirmed in immunoprecipitation assays. the oat3/pkczeta interaction was investigated in rodent renal cortical slices from fasted animals. insulin, an upstr ... | 2009 | 19028678 |
| doc2b: a novel syntaxin-4 binding protein mediating insulin-regulated glut4 vesicle fusion in adipocytes. | insulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily by stimulating the translocation of vesicles containing a facilitative glucose transporter, glut4, from intracellular compartments to the plasma membrane. the formation of stable soluble n-ethyl-maleimide-sensitive fusion protein [nsf] attachment protein receptor (snare) complexes between vesicle-associated membrane protein-2 (vamp-2) and syntaxin-4 initiates glut4 vesicle docking and fusion processes. additional ... | 2009 | 19033398 |
| functional characterization of the rad51d e233g genetic variant. | rad51d, a paralog of the mammalian rad51 gene, is an important component for dna repair and telomere maintenance. a rad51d variant, e233g, was initially identified as a potential susceptibility allele in high-risk, site-specific, familial breast cancer. we describe in this report, the effects of this amino acid change on rad51d protein interaction and function. | 2009 | 19033885 |
| vac14 nucleates a protein complex essential for the acute interconversion of pi3p and pi(3,5)p(2) in yeast and mouse. | the signalling lipid pi(3,5)p(2) is generated on endosomes and regulates retrograde traffic to the trans-golgi network. physiological signals regulate rapid, transient changes in pi(3,5)p(2) levels. mutations that lower pi(3,5)p(2) cause neurodegeneration in human patients and mice. the function of vac14 in the regulation of pi(3,5)p(2) was uncharacterized previously. here, we predict that yeast and mammalian vac14 are composed entirely of heat repeats and demonstrate that vac14 exerts an effect ... | 2008 | 19037259 |
| insig regulates hmg-coa reductase by controlling enzyme phosphorylation in fission yeast. | insig functions as a central regulator of cellular cholesterol homeostasis by controlling activity of hmg-coa reductase (hmgr) in cholesterol synthesis. insig both accelerates the degradation of hmgr and suppresses hmgr transcription through the srebp-scap pathway. the fission yeast schizosaccharomyces pombe encodes homologs of insig, hmgr, srebp, and scap, called ins1(+), hmg1(+), sre1(+), and scp1(+). here, we characterize fission yeast insig and demonstrate that ins1 is dedicated to regulatio ... | 2008 | 19041767 |
| diffusion magnetic resonance imaging: an imaging treatment response biomarker to chemoradiotherapy in a mouse model of squamous cell cancer of the head and neck. | for the treatment of squamous cell cancer of the head and neck (scchn), the assessment of treatment response is traditionally accomplished by volumetric measurements and has been suggested to be prognostic for an eventual response to treatment. an early evaluation response during the course of radiation therapy could provide an opportunity to tailor treatment to individual patients. diffusion magnetic resonance imaging (mri) allows for the quantification of tissue water diffusion values, thus tr ... | 2008 | 19043529 |
| recruitment of rna polymerase ii cofactor pc4 to dna damage sites. | the multifunctional nuclear protein positive cofactor 4 (pc4) is involved in various cellular processes including transcription, replication, and chromatin organization. recently, pc4 has been identified as a suppressor of oxidative mutagenesis in escherichia coli and saccharomyces cerevisiae. to investigate a potential role of pc4 in mammalian dna repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. we found a clear ac ... | 2008 | 19047459 |
| scavenger receptor collectin placenta 1 (cl-p1) predominantly mediates zymosan phagocytosis by human vascular endothelial cells. | collectin placenta 1 (cl-p1), a recently discovered scavenger receptor, mediates the uptake of oxidized low density lipoprotein and microbes. in this study, we investigated cl-p1-mediated binding and ingestion of yeast-derived zymosan bioparticles using chinese hamster ovary (cho) cells stably expressing human cl-p1 (cho/cl-p1) and human vascular endothelial cells constitutively expressed cl-p1. the uptake of zymosan by cho/cl-p1 was dependent upon the level of cl-p1 expressed on the membrane an ... | 2009 | 19073604 |
| regulation of forkhead transcription factor foxo3a contributes to calorie restriction-induced prevention of alzheimer's disease-type amyloid neuropathology and spatial memory deterioration. | forkhead transcription factor foxo3a, also known as daf-16 in caenorhabditis elegans, is a key regulator of the insulin receptor (ir)/insulin-like growth factor-i signaling pathway mediated extension of life span in worms and yeast. in this study, we report that calorie restriction (cr)-mediated activation of the ir signaling pathway leads to hyperphosphorylation of foxo3a transcription factor and, consequently, its exclusion from the nucleus. this inactivation of foxo3a activity is correlated w ... | 2008 | 19076455 |
| buffering by gene duplicates: an analysis of molecular correlates and evolutionary conservation. | one mechanism to account for robustness against gene knockouts or knockdowns is through buffering by gene duplicates, but the extent and general correlates of this process in organisms is still a matter of debate. to reveal general trends of this process, we provide a comprehensive comparison of gene essentiality, duplication and buffering by duplicates across seven bacteria (mycoplasma genitalium, bacillus subtilis, helicobacter pylori, haemophilus influenzae, mycobacterium tuberculosis, pseudo ... | 2008 | 19087332 |
| research on animal model organisms funded by the european commission's framework programmes. | recognising the crucial role of model organisms in exploring the causes of human disease and in developing safe treatments, the european commission has invested euro180 million in collaborative research projects on model organisms since 2002. further financial support is planned for the future. projects supported by the european commission are playing an important role in structuring the research landscape in europe and creating the knowledge base to understand health and disease. furthermore, t ... | 2008 | 19093026 |
| shd1 is a novel cytokine-inducible, negative feedback regulator of stat5-dependent transcription. | stat5 is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. during a search for stat5-interacting proteins, we identified shd1, a mammalian homologue of yeast gene sac3, as a potential interacter. shd1 was localized in the nucleus, and induced by cytokines that activate stat5, such as erythropoietin, interleukin-2 (il-2), or il-3. shd1 interacted specifically with stat5a and stat5b, and interestingly, it specif ... | 2009 | 18838617 |
| acheron, an novel la antigen family member, binds to cask and forms a complex with id transcription factors. | acheron, a lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the moth manduca sexta. acheron is phylogenetically-conserved and represents a new sub-family of lupus antigen proteins. acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. using acheron as bait, we performed a yeast two-hybrid screen with a mouse embr ... | 2009 | 19096764 |
| zinc finger transcription factor insm1 interrupts cyclin d1 and cdk4 binding and induces cell cycle arrest. | insm1 is a zinc finger transcription factor that plays an important role in pancreatic beta-cell development. to further evaluate its role in cell fate determination, we investigated insm1 effects on cell cycle function. the cyclin box of cyclin d1 is essential for insm1 binding. competitive pull-down and co-immunoprecipitation revealed that insm1 binding to cyclin d1 interrupts its association with cdk4 and induces hypophosphorylation of the retinoblastoma protein. an inducible tet-on system wa ... | 2009 | 19124461 |
| bacteriophage mu integration in yeast and mammalian genomes. | genomic parasites have evolved distinctive lifestyles to optimize replication in the context of the genomes they inhabit. here, we introduced new dna into eukaryotic cells using bacteriophage mu dna transposition complexes, termed 'transpososomes'. following electroporation of transpososomes and selection for marker gene expression, efficient integration was verified in yeast, mouse and human genomes. although mu has evolved in prokaryotes, strong biases were seen in the target site distribution ... | 2008 | 18953026 |
| chromosomal characterization and localization of the nad+-dependent histone deacetylase gene sirtuin 1 in the mouse. | sirtuin 1 (sirt1) is a nicotinamide adenine dinucleotide (nad+)-dependent deacetylase, which belongs to the silent information regulator 2 (sir2) family of histone deacetylases (hdacs). the yeast sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, dna repair and recombination, the cell cycle, microtubule organization, and in the regulation of aging. we isolated and characterized the murine sirt1 genomic sequence, which spans 19,910 bp and has one single g ... | 2009 | 19148549 |
| transcript elongation factor tfiis is involved in arabidopsis seed dormancy. | transcript elongation factor tfiis promotes efficient transcription by rna polymerase ii, since it assists in bypassing blocks during mrna synthesis. while yeast cells lacking tfiis are viable, inactivation of mouse tfiis causes embryonic lethality. here, we have identified a protein encoded in the arabidopsis genome that displays a marked sequence similarity to tfiis of other organisms, primarily within domains ii and iii in the c-terminal part of the protein. tfiis is widely expressed in arabi ... | 2009 | 19150360 |
| a protein complex that regulates ptdins(3,5)p2 levels. | phosphatidylinositol 3,5-bisphosphate (ptdins(3,5)p2) is needed for retrograde membrane trafficking from lysosomal and late endosomal compartments and its synthesis is tightly regulated. but how cells regulate ptdins(3,5)p2 synthesis--for example, in response to hyperosmotic shock--remains unexplained. a paper from the weisman group gives the most complete picture so far of a multiprotein complex that controls ptdins(3,5)p2 synthesis and explains how a vac14 mutation functionally impairs the sca ... | 2009 | 19158662 |
| insulin/igf-like signalling, the central nervous system and aging. | enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast saccharomyces, the fruit fly drosophila melanogaster, the nematode worm caenorhabditis elegans and the mouse. iis [insulin/igf (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. the pathway has diverse functions in multicell ... | 2009 | 19159343 |
| regulation of interleukin-12/interleukin-23 production and the t-helper 17 response in humans. | interleukin-12 (il-12) and il-23 share a common chain. yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. il-12 is involved in the induction or amplification of the t-helper (th) type 1 response, whereas il-23 has been associated with the generation of the th17 response and il-17 production. mycobacterium tuberculosis and yeast zymosan induce il-23, but in the absence of other stimuli, no il-12 is induced in human de ... | 2008 | 19161420 |
| p31 deficiency influences endoplasmic reticulum tubular morphology and cell survival. | p31, the mammalian orthologue of yeast use1p, is an endoplasmic reticulum (er)-localized soluble n-ethylmaleimide-sensitive factor attachment protein (snap) receptor (snare) that forms a complex with other snares, particularly syntaxin 18. however, the role of p31 in er function remains unknown. to determine the role of p31 in vivo, we generated p31 conditional knockout mice. we found that homozygous deletion of the p31 gene led to early embryonic lethality before embryonic day 8.5. conditional ... | 2009 | 19188447 |
| gene cloning and expression of pyridoxal 5'-phosphate-dependent l-threo-3-hydroxyaspartate dehydratase from pseudomonas sp. t62, and characterization of the recombinant enzyme. | l-threo-3-hydroxyaspartate dehydratase (l-tha dh, ec 4.3.1.16), which catalyses the cleavage of l-threo-3-hydroxyaspartate (l-tha) to oxalacetate and ammonia, has been purified from the soil bacterium pseudomonas sp. t62. in this report, the gene encoding l-tha dh was cloned and expressed in escherichia coli, and the gene product was purified and characterized in detail. a 957-bp nucleotide fragment was confirmed to be the gene encoding l-tha dh, based on the agreement of internal amino acid seq ... | 2009 | 19193709 |
| strong inducible knockdown of apc/ccdc20 does not cause mitotic arrest in human somatic cells. | the anaphase-promoting complex/cyclosome (apc/c) is a conserved ubiquitin ligase controlling mitosis and g1 phase of the cell cycle. the apc/c is activated by two regulatory subunits cdc20 (apc/c(cdc20)) and cdh1 (apc/c(cdh1)) to target securin, mitotic cyclins and other cell cycle regulatory proteins. cdc20 is essential for sister chromatid separation at the meta- to anaphase transition in yeast, drosophila and perhaps mouse embryos. however, whether cdc20 is essential for mitotic control of hu ... | 2009 | 19197151 |
| procedure for identification and characterization of drugs efficient against mammalian prion: from a yeast-based antiprion drug screening assay to in vivo mouse models. | prion diseases are fatal and incurable infectious neurodegenerative disorders affecting humans and other mammals. prions are composed essentially if not solely of prp(sc), a misfolded form of the host-encoded prp protein. prp(sc) catalyzes the transconformation of the normal endogenous prp (prp(c)) into more prp(sc). prion replication thus corresponds to the propagation of an altered folding state of prp. several prion proteins have also been identified in the simple model organism saccharomyces ... | 2009 | 19200013 |
| efficient and robust prediction algorithms for protein complexes using gomory-hu trees. | two-hybrid (y2h) protein-protein interaction (ppi) data suffer from high false positive and false negative rates, thus making searching for protein complexes in ppi networks a challenge. to overcome these limitations, we propose an efficient approach which measures connectivity between proteins not by edges, but by edge-disjoint paths. we model the number of edge-disjoint paths as a network flow and efficiently represent it in a gomory-hu tree. by manipulating the tree, we are able to isolate gr ... | 2009 | 19209703 |
| predicting the proportion of essential genes in mouse duplicates based on biased mouse knockout genes. | in the yeast or nematode, the proportion of essential genes in duplicates is lower than in singletons (single-copy genes), due to the functional redundancy. one may expect that it should be the same in the mouse genome. however, based on the publicly available mouse knockout data, it was observed that the proportion of essential genes in duplicates is similar to that in singletons. the most straightforward interpretation, as claimed in a recent study, is that duplicate genes may have a negligibl ... | 2008 | 19005716 |
| egf receptor signaling is involved in expression of osmoprotective tonebp target gene aldose reductase under hypertonic conditions. | renal medullary cells adapt to their hyperosmotic environment by enhanced expression of various osmoprotective genes. although it is clearly established that tonebp contributes to the expression of these genes, neither the precise signaling mechanism by which hypertonicity activates tonebp is completely understood, nor is it known whether a membrane-bound osmosenser, corresponding to yeast and bacteria, is present in mammalian cells. we found evidence that metalloproteinase (mmp)-dependent activ ... | 2009 | 19225051 |
| caml loss causes anaphase failure and chromosome missegregation. | calcium modulating cyclophilin ligand (caml) is a ubiquitously expressed cytoplasmic protein that is implicated in the egfr and lck signaling pathways and required for early embryonic and thymocyte development. to further define the critical biological functions of caml at the cellular level, we generated caml-deleted mouse embryonic fibroblasts (mefs) using an in vitro cre-loxp mediated conditional knockout system. we found that caml(-/-) mefs have severely impaired proliferation and a strong r ... | 2009 | 19229138 |
| protein kinase ck2 interacts with adiponectin receptor 1 and participates in adiponectin signaling. | adiponectin is an adipokine with anti-atherogenic, anti-diabetic and insulin sensitizing properties. its effects on energy homeostasis, glucose and lipid metabolism are mediated by two ubiquitously expressed seven-transmembrane receptors, adipor1 and -r2. with the exception of appl1 and rack1, no intracellular binding partners of adiponectin receptors are reported and thus signaling pathways downstream of these receptors remain largely unknown. to incorporate adiponectins protective potential in ... | 2009 | 19233263 |
| mammalian cell display for antibody engineering. | antibody engineering has generally been carried out by displaying mouse or human antibodies or antibody fragments on the surface of microorganisms (phage, bacteria, and yeast). we have shown that mammalian cells can be used to display single-chain antibody fragments (scfvs) for affinity maturation. using mammalian cell display one can isolate and engineer scfvs, fabs, or whole iggs for increased affinity and other specific biological functions. here, we describe a mammalian cell display strategy ... | 2009 | 19252852 |
| p4 atpases - lipid flippases and their role in disease. | p4 atpases (type 4 p-type atpases) are multispan transmembrane proteins that have been implicated in phospholipid translocation from the exoplasmic to the cytoplasmic leaflet of biological membranes. studies in saccharomyces cerevisiae have indicated that p4 atpases are important in vesicle biogenesis and are required for vesicular trafficking along several intracellular vesicular transport routes. although little is known about mammalian p4 atpases, some members of this subfamily appear to be a ... | 2009 | 19254779 |
| sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging. | mammalian sirtuins, sirt1-sirt7, are recently discovered regulatory proteins, which play decisive roles in cellular metabolism, stress resistance, and proliferation. sirtuins are homologs of the founder member of the sirtuin family, the yeast sir2. sir2 encodes a nad(+)-dependent histone deacetylase and its overexpression extends the lifespan through silencing of specific chromatin regions. lifespan extension by sir2 homologs was also demonstrated in more complex species such as c. elegans and d ... | 2008 | 19261981 |
| liquiritigenin, a licorice flavonoid, helps mice resist disseminated candidiasis due to candida albicans by th1 immune response, whereas liquiritin, its glycoside form, does not. | licorice (the root of glycyrrhizae plant) has been used as an oriental herbal medicine for thousands of years. the licorice flavonoid components are reported to possess immunomodulatory activities. in this present study, we investigated the immunomodulatory effects of liquiritigenin (lg) and liquiritin (lq), licorice flavonoid components, against disseminated candidiasis due to candida albicans, a dimorphic fungus, that causes severe disease via hematogenous dissemination and local diseases such ... | 2009 | 19264152 |
| the outcome of cryptococcus neoformans intracellular pathogenesis in human monocytes. | cryptococcus neoformans is an encapsulated yeast that is a facultative intracellular pathogen. the interaction between macrophages and c. neoformans is critical for extrapulmonary dissemination of this pathogenic yeast. c. neoformans can either lyse macrophages or escape from within them through a process known as phagosomal extrusion. however, most studies of intracellular pathogenesis have been made with mouse cells and their relevance to human infection is uncertain. in this study we extended ... | 2009 | 19265539 |
| identifying critical non-catalytic residues that modulate protein kinase a activity. | distal interactions between discrete elements of an enzyme are critical for communication and ultimately for regulation. however, identifying the components of such interactions has remained elusive due to the delicate nature of these contacts. protein kinases are a prime example of an enzyme with multiple regulatory sites that are spatially separate, yet communicate extensively for tight regulation of activity. kinase misregulation has been directly linked to a variety of cancers, underscoring ... | 2009 | 19270744 |
| identification of atg5-dependent transcriptional changes and increases in mitochondrial mass in atg5-deficient t lymphocytes. | autophagy is implicated in many functions of mammalian cells such as organelle recycling, survival and differentiation, and is essential for the maintenance of t and b lymphocytes. here, we demonstrate that autophagy is a constitutive process during t cell development. deletion of the essential autophagy genes atg5 or atg7 in t cells resulted in decreased thymocyte and peripheral t cell numbers, and atg5-deficient t cells had a decrease in cell survival. we employed functional-genetic and integr ... | 2009 | 19276668 |
| the complex relationship of gene duplication and essentiality. | in yeast and worm, duplicate genes overlap in function so that deleting one of a pair from the genome is less likely to be lethal than deleting a singleton gene. by contrast, previous analyses showed that mouse duplicate genes were as essential as singletons. we show that the relationship between gene duplication and essentiality is complex in multicellular organisms, with developmental genes and genes that were duplicated by whole genome duplication being more essential than other duplicated ge ... | 2009 | 19285746 |
| identifying components of the hair-cell interactome involved in cochlear amplification. | although outer hair cells (ohcs) play a key role in cochlear amplification, it is not fully understood how they amplify sound signals by more than 100 fold. two competing or possibly complementary mechanisms, stereocilia-based and somatic electromotility-based amplification, have been considered. lacking knowledge about the exceptionally rich protein networks in the ohc plasma membrane, as well as related protein-protein interactions, limits our understanding of cochlear function. therefore, we ... | 2009 | 19320974 |
| a top-down approach to infer and compare domain-domain interactions across eight model organisms. | knowledge of specific domain-domain interactions (ddis) is essential to understand the functional significance of protein interaction networks. despite the availability of an enormous amount of data on protein-protein interactions (ppis), very little is known about specific ddis occurring in them. here, we present a top-down approach to accurately infer functionally relevant ddis from ppi data. we created a comprehensive, non-redundant dataset of 209,165 experimentally-derived ppis by combining ... | 2009 | 19333396 |
| enhanced genomic instabilities caused by deregulated microtubule dynamics and chromosome segregation: a perspective from genetic studies in mice. | aneuploidy is defined as numerical abnormalities of chromosomes and is frequently (>90%) present in solid tumors. in general, tumor cells become increasingly aneuploid with tumor progression. it has been proposed that enhanced genomic instability at least contributes significantly to, if not requires, tumor progression. two major modes for genomic instability are microsatellite instability (min) and chromosome instability (cin). min is associated with dna-level defects (e.g. mismatch repair defe ... | 2009 | 19372138 |
| piplartine induces genotoxicity in eukaryotic but not in prokaryotic model systems. | piplartine {5,6-dihydro-1-[(2e)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propen-1-yl]-2(1h)-pyridinone} is an alkamide present in piper species that exhibits promising anticancer properties. it was previously shown that piplartine is mutagenic in yeast and cultured mammalian cells. this study was performed to increase the knowledge on the mutagenic potential of piplartine using the salmonella/microsome assay, v79 cell micronucleus and chromosome aberration assays, and mouse bone-marrow micronucleus te ... | 2009 | 19379832 |
| a long-lasting, plasmin-activatable thrombin inhibitor aids clot lysis in vitro and does not promote bleeding in vivo. | the leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin's rapid clearance from the circulation. we previously employed albumin fusion to slow hirudin variant 3 (hv3) clearance. in this study, we hypothesized that reconfiguration of the chimera, appending human serum albumin (hsa) to the n-terminus of hv3, with an intervening plasmin cleavage site, would create a slowly cleared, plasmin-ac ... | 2009 | 19404540 |
| transcriptional activities of the pax6 gene eyeless regulate tissue specificity of ectopic eye formation in drosophila. | pax genes encode dna binding proteins that play pivotal roles in the determination of complex tissues. members of one subclass, pax6, function as selector genes and play key roles in the retinal development of all seeing animals. mutations within the pax6 homologs including fly eyeless, mouse small eye and human pax6 lead to severe retinal defects in their respective systems. in drosophila eyeless and twin of eyeless, play non-redundant roles in the developing retina. one particularly interestin ... | 2009 | 19406113 |
| the secret message of heterochromatin: new insights into the mechanisms and function of centromeric and pericentric repeat sequence transcription. | in the fission yeast, s. pombe, small dsrna generated by rnai-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. the existence of conserved features within the general organization of centromeric and pericentromeric repeats in yeast, mouse and human argues in favor of a conserved role for centromeric and pericentromeric-derived transcripts across these species. in support of this, evidence is accumulating that centromeric and pericentromeric sequen ... | 2009 | 19412885 |
| mitochondrial clearance is regulated by atg7-dependent and -independent mechanisms during reticulocyte maturation. | mitochondrial clearance is a well recognized but poorly understood biologic process, and reticulocytes, which undergo programmed mitochondrial clearance, provide a useful model to study this phenomenon. at the ultrastructural level, mitochondrial clearance resembles an autophagy-related process; however, the role of autophagy in mitochondrial clearance has not been established. here we provide genetic evidence that autophagy pathways, initially identified in yeast, are involved in mitochondrial ... | 2009 | 19417210 |
| nutrient-dependent mtorc1 association with the ulk1-atg13-fip200 complex required for autophagy. | autophagy is an intracellular degradation system, by which cytoplasmic contents are degraded in lysosomes. autophagy is dynamically induced by nutrient depletion to provide necessary amino acids within cells, thus helping them adapt to starvation. although it has been suggested that mtor is a major negative regulator of autophagy, how it controls autophagy has not yet been determined. here, we report a novel mammalian autophagy factor, atg13, which forms a stable approximately 3-mda protein comp ... | 2009 | 19211835 |
| papa-1 is a nuclear binding partner of igfbp-2 and modulates its growth-promoting actions. | igf-binding proteins (igfbps) have multiple cellular effects, which occur by both igf-dependent and -independent mechanisms. igfbp-2 is involved in the regulation of both normal and carcinogenic cell growth. to further understand the actions of igfbp-2, we carried out a yeast two-hybrid screen to search for intracellular partner proteins using a human prostate cdna library. we isolated pim-1-associated protein-1 (pap-1)-associated protein-1 (papa-1) as an igfbp-2-binding protein, whose expressio ... | 2009 | 19095771 |
| identification of proteins interacting with selenocysteine lyase. | yeast two-hybrid screening of mouse cdna libraries was performed to identify proteins interacting with selenocysteine lyase (scl), which decomposes l-selenocysteine. several proteins related to spermatogenesis, protein synthesis, and cell viability/apoptosis were identified as potential interactors. major urinary proteins 1 and 2 interacted with scl and inhibited its activity. coimmunoprecipitation revealed interactions between scl and each of two selenophosphate synthetase isozymes. | 2009 | 19420685 |
| paracoccidioides brasiliensis pancreatic destruction in calomys callosus experimentally infected. | the wild rodent calomys callosus is notably resistant to trypanosoma cruzi infection. in order to better characterize this animal model for experimental infections, we inoculated c. callosus intraperitoneally with paracoccidioides brasiliensis, a thermally dimorphic fungus that causes a chronic disease with severe granuloma formation in the mouse and humans. the dissemination of p. brasiliensis cells through the lungs, liver, pancreas, and spleen was assessed by histological analysis. | 2009 | 19422699 |
| n-acetyl cysteine protects against ionizing radiation-induced dna damage but not against cell killing in yeast and mammals. | ionizing radiation (ir) induces dna strand breaks leading to cell death or deleterious genome rearrangements. in the present study, we examined the role of n-acetyl-l-cysteine (nac), a clinically proven safe agent, for it's ability to protect against gamma-ray-induced dna strand breaks and/or dna deletions in yeast and mammals. in the yeast saccharomyces cerevisiae, dna deletions were scored by reversion to histidine prototrophy. human lymphoblastoid cells were examined for the frequency of gamm ... | 2009 | 19427509 |
| the intestinal trefoil factor (tff3), also expressed in the inner ear, interacts with peptides contributing to apoptosis. | the 3 members of the mammalian trefoil factor family (tff) are expressed and secreted as cytoprotective peptides along the entire length of the normal gastrointestinal tract. more recently, they were shown to display multifunctional properties. goblet cells of the small and large intestine constitute a major source for the synthesis of the third family member, tff3 (formerly intestinal trefoil factor, itf). tff3, like the other family members, is rapidly up-regulated in response to physical woun ... | 2009 | 19433915 |
| production of catalytically inactive bont/a1 holoprotein and comparison with bont/a1 subunit vaccines against toxin subtypes a1, a2, and a3. | a recombinant, catalytically inactive clostridium botulinum neurotoxin a1 holoprotein (cibont/a1 hp) was constructed by introducing amino acid substitutions h223a, e224a, and h227a in the active site to ablate proteolytic activity. cibont/a1 hp was produced in the yeast pichia pastoris and the purified product was evaluated as a vaccine candidate by comparison against recombinant bont/a1 lc, lc-belt, lc-h(n), and h(c) antigens and a lc-h(n)+h(c) combination in mouse potency and efficacy bioassay ... | 2009 | 19450643 |
| what was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor? | ubiquitin (ub)-conjugating enzymes (e2) are key enzymes in ubiquitination or ub-like modifications of proteins. we searched for all proteins belonging to the e2 enzyme super-family in seven species (homo sapiens, mus musculus, drosophila melanogaster, caenorhabditis elegans, schizosaccharomyces pombe, saccharomyces cerevisiae, and arabidopsis thaliana) to identify families and to reconstruct each family's phylogeny. our phylogenetic analysis of 207 genes led us to define 17 e2 families, with 37 ... | 2009 | 19452197 |
| inference of gene pathways using mixture bayesian networks. | inference of gene networks typically relies on measurements across a wide range of conditions or treatments. although one network structure is predicted, the relationship between genes could vary across conditions. a comprehensive approach to infer general and condition-dependent gene networks was evaluated. this approach integrated bayesian network and gaussian mixture models to describe continuous microarray gene expression measurements, and three gene networks were predicted. | 2009 | 19454027 |
| candida albicans cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models. | candida albicans is the most common human fungal pathogen, yet the pathogenesis of c. albicans infection remains incompletely understood. we hypothesized that c. albicans has developed evolutionarily conserved mechanisms to invade disparate hosts and tested whether toll mutant flies could serve as a model host for high-throughput screening of c. albicans virulence genes. we screened 34 c. albicans mutants defective in putative transcription factor genes (see http://www.tigr.org/tigr-scripts/e2k1 ... | 2009 | 19463063 |
| mouse models of altered protein kinase a signaling. | protein kinase a (pka) is an evolutionarily conserved protein which has been studied in model organisms from yeast to man. although the camp-pka signaling system was the first mammalian second messenger system to be characterized, many aspects of this pathway are still not well understood. owing to findings over the past decade implicating pka signaling in endocrine (and other) tumorigenesis, there has been renewed interest in understanding the role of this pathway in physiology, particularly as ... | 2009 | 19470615 |
| small rnas derived from snornas. | small nucleolar rnas (snornas) guide rna modification and are localized in nucleoli and cajal bodies in eukaryotic cells. components of the rna silencing pathway associate with these structures, and two recent reports have revealed that a human and a protozoan snorna can be processed into mirna-like rnas. here we show that small rnas with evolutionary conservation of size and position are derived from the vast majority of snorna loci in animals (human, mouse, chicken, fruit fly), arabidopsis, an ... | 2009 | 19474147 |
| mitofusins and opa1 mediate sequential steps in mitochondrial membrane fusion. | mitochondrial fusion requires the coordinated fusion of the outer and inner membranes. three large gtpases--opa1 and the mitofusins mfn1 and mfn2--are essential for the fusion of mammalian mitochondria. opa1 is mutated in dominant optic atrophy, a neurodegenerative disease of the optic nerve. in yeast, the opa1 ortholog mgm1 is required for inner membrane fusion in vitro; nevertheless, yeast lacking mgm1 show neither outer nor inner membrane fusion in vivo, because of the tight coupling between ... | 2009 | 19477917 |
| family classification without domain chaining. | motivation: classification of gene and protein sequences into homologous families, i.e. sets of sequences that share common ancestry, is an essential step in comparative genomic analyses. this is typically achieved by construction of a sequence homology network, followed by clustering to identify dense subgraphs corresponding to families. accurate classification of single domain families is now within reach due to major algorithmic advances in remote homology detection and graph clustering. howe ... | 2009 | 19478015 |
| immunohistochemical detection of dysbindin at the astroglial endfeet around the capillaries of mouse brain. | dysbindin was first identified by the yeast two hybrid assay as a binding partner of dystrobrevin which is a cytoplasmic member of dystrophin glycoprotein complex. immunolocalization of dystrobrevin in the astrocyte endfeet and endothelial cells in the rat cerebellum was reported. therefore, we were interested in the expression and localization of dystrobrevin binding protein dysbindin in the mouse brain capillary wall and its surrounding astroglial endfeet. we examined whether the dysbindin exp ... | 2009 | 19495999 |
| anti-edema effects of brown seaweed (undaria pinnatifida) extract on phorbol 12-myristate 13-acetate-induced mouse ear inflammation. | the brown seaweed undaria pinnatifida (harvey) suringar is used in traditional medicine to treat fever, urination problems, lumps and swelling, and as a dietary supplement for post-childbirth women. we examined the anti-inflammatory activities of the seaweed. the methanol extract of the seaweed was active against mouse ear edema induced by phorbol myristate acetate (pma), with an ic(50) of 10.3 mg/ml. the extract reduced the edema to a half-maximal level when applied at the concentration of 40 m ... | 2009 | 19507279 |
| fungal zymosan and mannan activate the cryopyrin inflammasome. | some fungal species are opportunistic pathogens that can cause infection in people with compromised immune systems. activation of caspase-1 and the subsequent secretion of mature interleukin (il)-1beta is a major signaling pathway of the innate immune system, but how yeasts induce caspase-1 activation is unknown. we show here that stimulation of macrophages and dendritic cells with heat-killed saccharomyces cerevisiae or the purified cell wall components zymosan and mannan induced caspase-1 acti ... | 2009 | 19509280 |
| golph3 modulates mtor signalling and rapamycin sensitivity in cancer. | genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). here, using integrative analysis of a genomic profile of the region, we identify a golgi protein, golph3, as a candidate targeted for amplification. gain- and loss-of-function studies in vitro and in vivo validated golph3 as a potent oncogene. physically, golph3 localizes to the trans-golgi ... | 2009 | 19553991 |
| grp94, the endoplasmic reticulum hsp90, has a similar solution conformation to cytosolic hsp90 in the absence of nucleotide. | the molecular chaperone, hsp90, is an essential eukaryotic protein that assists in the maturation and activation of client proteins. hsp90 function depends upon the binding and hydrolysis of atp, which causes large conformational rearrangements in the chaperone. hsp90 is highly conserved from bacteria to eukaryotes, and similar nucleotide-dependent conformations have been demonstrated for the bacterial, yeast, and human proteins. there are, however, important species-specific differences in the ... | 2009 | 19554567 |
| ebola zaire virus blocks type i interferon production by exploiting the host sumo modification machinery. | ebola zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in africa. the virus replicates in macrophages and dendritic cells (dcs), suppressing production of type i interferons (ifns) while inducing the release of large quantities of proinflammatory cytokines. although the viral vp35 protein has been shown to inhibit ifn responses, the mechanism by which it blocks ifn production has not been fully elucidated. we expressed vp35 from a mouse-ada ... | 2009 | 19557165 |
| slimmer (fhl1b/kyot3) interacts with the proapoptotic protein siva-1 (cd27bp) and delays skeletal myoblast apoptosis. | the fhl1 gene encoding four-and-a-half lim protein-1 (fhl1) and its spliced isoform, slimmer, is mutated in reducing body myopathy, x-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome. in this study we have identified a novel function for slimmer in delaying skeletal muscle apoptosis via an interaction with the proapoptotic protein siva-1. siva-1 was identified as a slimmer-specific-interacting protein using yeast two-hybrid screening, direct-bindin ... | 2009 | 19643733 |
| probing for primary functions of prohibitin in trypanosoma brucei. | prohibitins (phbs) 1 and 2 are small conserved proteins implicated in a number of functions in the mitochondrion, as well as in the nucleus of eukaryotic cells. the current understanding of phb functions comes from studies of model organisms such as yeast, worm and mouse, but considerable debate remains with regard to the primary functions of these ubiquitous proteins. we exploit the tractable reverse genetics of trypanosoma brucei, the causative agent of african sleeping sickness, in order to s ... | 2010 | 19683530 |
| cutting edge: candida albicans hyphae formation triggers activation of the nlrp3 inflammasome. | the proinflammatory cytokine il-1beta plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger il-1beta secretion are unclear. in this study we show that infection with candida albicans is sensed by the nlrp3 inflammasome, resulting in the subsequent release of il-1beta. the ability of c. albicans to switch from a unicellular yeast form into a filamentous form is essential for activation of the nlrp3 inflammasome, as c. albicans mutants incapable ... | 2009 | 19684085 |
| mapping the interaction site of prion protein and sho. | the cellular prion protein (prp(c)) is a highly conserved protein among mammals and is considered to have important cellular functions. despite decades of intensive research, however, the physiological function of prp(c) remains unclear. sho (shadoo, shadow of prion protein) and prp(c) have similar n-terminals, which suggests that the two proteins share biological functions. using truncation mutants of both proteins and yeast two-hybrid analysis, with validation by co-immunoprecipitation and sur ... | 2010 | 19685161 |
| nascent: an automatic protein interaction network generation tool for non-model organisms. | large quantity of reliable protein interaction data are available for model organisms in public depositories (e.g., mint, dip, hprd, interact). most data correspond to experiments with the proteins of saccharomyces cerevisiae, drosophila melanogaster, homo sapiens, caenorhabditis elegans, escherichia coli and mus musculus. for other important organisms the data availability is poor or non-existent. here we present nascent, a completely automatic web-based tool and also a downloadable java progra ... | 2009 | 19707301 |
| interaction of postsynaptic density protein-95 with nmda receptors influences excitotoxicity in the yeast artificial chromosome mouse model of huntington's disease. | evidence suggests that nmda-type glutamate receptors contribute to degeneration of striatal medium-sized spiny neurons (msns) in huntington's disease (hd). previously, we demonstrated that nmda receptor (nmdar)-mediated current and/or toxicity is increased in msns from the yeast artificial chromosome (yac) transgenic mouse model expressing polyglutamine (polyq)-expanded (mutant) full-length human huntingtin (htt). others have shown that membrane-associated guanylate kinases (maguks), such as psd ... | 2009 | 19726651 |
| the inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes. | lysosomes are intracellular organelles which contain enzymes and activator proteins involved in the digestion and recycling of a variety of cellular and extracellular substances. we have identified a novel sorting receptor, sortilin, which is involved in the lysosomal trafficking of the sphingolipid activator proteins, prosaposin and gm(2)ap, and the soluble hydrolases cathepsin d, cathepsin h, and acid sphingomyelinase. sortilin belongs to a growing family of receptors with homology to the yeas ... | 2009 | 19732768 |
| pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide. | intravenous injection of lipopolysaccharide (lps, a component of the gram-negative bacterial cell-surface) or mannan (man, a component of the fungal cell-surface) into mice reportedly induces anaphylaxis-like shock (als) via complement-associated platelet degradation and platelet-activating factor (paf), respectively. however, it is unclear whether paf is involved in lps-als or whether complements and/or platelets are involved in man-als. here, using preparations of man from saccharomyces cerevi ... | 2009 | 19755175 |
| a role of helix 12 of the vitamin d receptor in smrt corepressor interaction. | to repress gene transcription, the unliganded nuclear receptor (nr) recruits the n-cor and smrt corepressors via its direct association with the conserved motif within bipartite nr-interaction domains (ids) of corepressors. we recently reported that smrt is directly involved in the vdr-mediated repression via an id1-specific interaction with the vdr. here we show that removal of helix 12 from vdr (vdrdeltaaf2) converts it to a more potent repressor through additional interaction between the vdr ... | 2009 | 19133230 |
| microkit 3.0: an integrated database of midbody, centrosome and kinetochore. | during cell division/mitosis, a specific subset of proteins is spatially and temporally assembled into protein super complexes in three distinct regions, i.e. centrosome/spindle pole, kinetochore/centromere and midbody/cleavage furrow/phragmoplast/bud neck, and modulates cell division process faithfully. although many experimental efforts have been carried out to investigate the characteristics of these proteins, no integrated database was available. here, we present the microkit database (http: ... | 2010 | 19783819 |
| nutrient control of torc1, a cell-cycle regulator. | it is well established that the target of rapamycin (tor) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. mammalian tor complex 1 (mtorc1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mtorc1 ... | 2009 | 19419870 |
| cooperative binding of two acetylation marks on a histone tail by a single bromodomain. | a key step in many chromatin-related processes is the recognition of histone post-translational modifications by effector modules such as bromodomains and chromo-like domains of the royal family. whereas effector-mediated recognition of single post-translational modifications is well characterized, how the cell achieves combinatorial readout of histones bearing multiple modifications is poorly understood. one mechanism involves multivalent binding by linked effector modules. for example, the tan ... | 2009 | 19794495 |
| the new yeast is a mouse! | | 2009 | 19419243 |
| limiting the persistence of a chromosome break diminishes its mutagenic potential. | to characterize the repair pathways of chromosome double-strand breaks (dsbs), one approach involves monitoring the repair of site-specific dsbs generated by rare-cutting endonucleases, such as i-scei. using this method, we first describe the roles of ercc1, msh2, nbs1, xrcc4, and brca1 in a set of distinct repair events. subsequently, we considered that the outcome of such assays could be influenced by the persistent nature of i-scei-induced dsbs, in that end-joining (ej) products that restore ... | 2009 | 19834534 |
| comparing effects of mtr and mtert deletion on gene expression and dna damage response: a critical examination of telomere length maintenance-independent roles of telomerase. | telomerase, the essential enzyme that maintains telomere length, contains two core components, tert and tr. early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. however, recent studies have suggested additional roles for telomerase components in transcription and the response to dna damage. to examine these potential telomere length maintenance-independent roles of telomerase components, we examined first ... | 2010 | 19850716 |
| identification of novel pten-binding partners: pten interaction with fatty acid binding protein fabp4. | pten is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. recent studies have also demonstrated that pten is a promising target in type ii diabetes and obesity treatment. using c-terminal pten sequence in peg202-nls as bait, yeast two-hybrid screening on mouse embryo, colon cancer, and hela cdna libraries was carried out. isolated positive clones were validated by mating assay and identified through automat ... | 2010 | 19911253 |
| an auxin-based degron system for the rapid depletion of proteins in nonplant cells. | plants have evolved a unique system in which the plant hormone auxin directly induces rapid degradation of the aux/iaa family of transcription repressors by a specific form of the scf e3 ubiquitin ligase. other eukaryotes lack the auxin response but share the scf degradation pathway, allowing us to transplant the auxin-inducible degron (aid) system into nonplant cells and use a small molecule to conditionally control protein stability. the aid system allowed rapid and reversible degradation of t ... | 2009 | 19915560 |
| balance between synaptic versus extrasynaptic nmda receptor activity influences inclusions and neurotoxicity of mutant huntingtin. | huntington's disease is caused by an expanded cag repeat in the gene encoding huntingtin (htt), resulting in loss of striatal and cortical neurons. given that the gene product is widely expressed, it remains unclear why neurons are selectively targeted. here we show the relationship between synaptic and extrasynaptic activity, inclusion formation of mutant huntingtin protein (mthtt) and neuronal survival. synaptic n-methyl-d-aspartate-type glutamate receptor (nmdar) activity induces mthtt inclus ... | 2009 | 19915593 |
| the role of scaffold proteins in jnk signalling. | this paper summarises how scaffold proteins affects and regulate the jnk signalling pathway. we believe that some of these scaffold proteins, by virtue of their anchoring and catalytic properties contribute to a high degree of specificity of intra cellular signalling pathways that regulate the progression through the cell cycle. | 2010 | 19922489 |
| accumulation of cd11b+ lung dendritic cells in response to fungal infection results from the ccr2-mediated recruitment and differentiation of ly-6chigh monocytes. | pulmonary clearance of the encapsulated yeast cryptococcus neoformans is associated with the ccr2-mediated accumulation of lung dendritic cells (dc) and the development of a t1 adaptive immune response. the objective of this study was to identify the circulating dc precursor(s) responsible for this large increase in lung dc numbers. an established murine model was used to evaluate putative dc precursors in the blood, bone marrow, and lungs of ccr2(+/+) mice and ccr2(-/-) mice throughout a time c ... | 2009 | 19933856 |
| production of novel antioxidative phenolic amides through heterologous expression of the plant's chlorogenic acid biosynthesis genes in yeast. | phenolic esters like chlorogenic acid play an important role in therapeutic properties of many plant extracts. we aimed to produce phenolic esters in baker's yeast, by expressing tobacco 4cl and globe artichoke hct. indeed yeast produced phenolic esters. however, the primary product was identified as n-(e)-p-coumaroyl-3-hydroxyanthranilic acid by nmr. this compound is an amide condensation product of p-coumaric acid, which was supplied to the yeast, with 3-hydroxyanthranilic acid, which was unex ... | 2010 | 19941969 |
| identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. | formins stimulate actin filament assembly for fundamental cellular processes including division, adhesion, establishing polarity, and motility. a formin inhibitor would be useful because most cells express multiple formins whose functions are not known and because metastatic tumor formation depends on the deregulation of formin-dependent processes. we identified a general small molecule inhibitor of formin homology 2 domains (smifh2) by screening compounds for the ability to prevent formin-media ... | 2009 | 19942139 |
| miz1 is a signal- and pathway-specific modulator or regulator (smor) that suppresses tnf-alpha-induced jnk1 activation. | the proinflammatory cytokine tnf-alpha exerts its pleiotropic functions through activation of multiple downstream effectors, including jnk1. yet, the underlying regulatory mechanism is incompletely understood. here, we report that the transcription factor myc-interacting zinc-finger protein 1 (miz1) selectively suppresses tnf-alpha-induced jnk1 activation and cell death independently of its transcription activity. proteomics analysis and yeast two-hybrid screening reveal that miz1 is a jnk-assoc ... | 2009 | 19815509 |
| mammalian rif1 contributes to replication stress survival and homology-directed repair. | rif1, originally recognized for its role at telomeres in budding yeast, has been implicated in a wide variety of cellular processes in mammals, including pluripotency of stem cells, response to double-strand breaks, and breast cancer development. as the molecular function of rif1 is not known, we examined the consequences of rif1 deficiency in mouse cells. rif1 deficiency leads to failure in embryonic development, and conditional deletion of rif1 from mouse embryo fibroblasts affects s-phase pro ... | 2009 | 19948482 |