Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
zip4h (tex11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over.we have recently shown that hypomorphic mre11 complex mouse mutants exhibit defects in the repair of meiotic double strand breaks (dsbs). this is associated with perturbation of synaptonemal complex morphogenesis, repair and regulation of crossover formation. to further assess the mre11 complex's role in meiotic progression, we identified testis-specific nbs1-interacting proteins via two-hybrid screening in yeast. in this screen, zip4h (tex11), a male germ cell specific x-linked gene was isolate ...200818369460
analysis of rho-gtpase mimicry by a family of bacterial type iii effector proteins.microbial pathogens may hijack the actin cytoskeleton machinery to facilitate actin-based motility, cellular invasion, and intracellular trafficking through the endocytic pathway. of particular interest has been a large class of virulence factors collectively termed the type iii "effector" proteins. following contact with a eukaryotic cell, gram-negative bacterial pathogens employ a dedicated protein secretion apparatus termed type iii to translocate effector proteins into the cellular cytoplasm ...200818374161
high resistance to oxidative stress in the fungal pathogen candida glabrata is mediated by a single catalase, cta1p, and is controlled by the transcription factors yap1p, skn7p, msn2p, and msn4p.we characterized the oxidative stress response of candida glabrata to better understand the virulence of this fungal pathogen. c. glabrata could withstand higher concentrations of h(2)o(2) than saccharomyces cerevisiae and even candida albicans. stationary-phase cells were extremely resistant to oxidative stress, and this resistance was dependent on the concerted roles of stress-related transcription factors yap1p, skn7p, and msn4p. we showed that growing cells of c. glabrata were able to adapt ...200818375620
the retinitis pigmentosa 2 gene product is a gtpase-activating protein for arf-like 3.the retinitis pigmentosa 2 (rp2) gene is responsible for a particular variant of x chromosome-linked eye disease. previously, rp2 was shown to bind the gtp form of the small g protein arf-like 3 (arl3), thus qualifying as an effector. here we present the arl3-gppnhp-rp2 complex structure, which shows features resembling complexes with gtpase-activating proteins (gaps). biochemical analysis showing a 90,000-fold stimulation of the gtpase reaction together with the structure of an arl3-gdp-alf4--r ...200818376416
alg-2 interacting protein aip1: a novel link between d1 and d3 signalling.dopamine signalling is a critically important process in the human brain that controls mood, cognition and motor activity. in order to gain detailed insight into this signalling pathway at the molecular level, we carried out yeast two-hybrid screens with d1-like (d1, d5) and d2-like (d2, d3, d4) dopamine receptors and identified 11 dopamine receptor interacting proteins (drips). using the c-terminal domain of d1 receptor as bait, we identified aip1 (alg-2 interacting protein 1), a known modulato ...200818380665
anti-serum albumin domain antibodies for extending the half-lives of short lived drugs.we have used phage display to isolate a range of human domain antibodies (dabs) that bind to mouse, rat and/or human serum albumin (sa) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. in contrast to non-sa-binding dabs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kda 'albudabs' can match the half-life of sa itself. to demonstrate the use of albudabs for extending the half-lives of therapeutic drugs, we created a fusion of ...200818387938
conserved c-terminal motifs required for avirulence and suppression of cell death by phytophthora sojae effector avr1b.the sequenced genomes of oomycete plant pathogens contain large superfamilies of effector proteins containing the protein translocation motif rxlr-deer. however, the contributions of these effectors to pathogenicity remain poorly understood. here, we show that the phytophthora sojae effector protein avr1b can contribute positively to virulence and can suppress programmed cell death (pcd) triggered by the mouse bax protein in yeast, soybean (glycine max), and nicotiana benthamiana cells. we ident ...200818390593
interaction of rab3b with microtubule-binding protein gas8 in nih 3t3 cells.rab3 subfamily small g proteins (rab3a, rab3b, rab3c, and rab3d) control the regulated exocytosis in neuronal/secretory cells. rab3b is also detected and upregulated in non-neuronal/non-secretory cells, whereas its function remains elusive. in the present study, we identified growth-arrest-specific gene 8 (gas8), an evolutionally conserved microtubule-binding protein that is upregulated in growth-arrested nih 3t3 cells and involved in the dynein motor regulation in flagellar/ciliary axoneme, as ...200818396146
phylogenetic distribution of large-scale genome patchiness.the phylogenetic distribution of large-scale genome structure (i.e. mosaic compositional patchiness) has been explored mainly by analytical ultracentrifugation of bulk dna. however, with the availability of large, good-quality chromosome sequences, and the recently developed computational methods to directly analyze patchiness on the genome sequence, an evolutionary comparative analysis can be carried out at the sequence level.200818405379
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
mapping the ruthenium red-binding site of the voltage-dependent anion channel-1.we have previously shown that ruthenium red (rur) binds to the voltage-dependent anion channel (vdac) in the outer mitochondrial membrane, decreasing channel conductance and protecting against apoptotic cell death. in this report, we define the murine and yeast vdac1 amino acid residues involved in the interaction with rur. binding of rur to bilayer-reconstituted mvdac1 and the resulting channel closure was inhibited upon mutation of specific vdac1 residues. rur protection against cell death, as ...200817590433
mtbp haploinsufficiency in mice increases tumor metastasis.mdm2 inhibits the function of the p53 tumor suppressor. mdm2 is overexpressed in many tumors with wild-type p53 suggesting an alternate mechanism of loss of p53 activity in tumors. an mdm2-binding protein (mtbp) was identified using a yeast two-hybrid screen. in tissue culture, mtbp inhibits mdm2 self-ubiquitination, leading to stabilization of mdm2 and increased degradation of p53. to address the role of mtbp in the regulation of the p53 pathway in vivo, we deleted the mtbp gene in mice. homozy ...200817906694
v-atpase v0 sector subunit a1 in neurons is a target of calmodulin.the v(0) complex forms the proteolipid pore of a vesicular atpase that acidifies vesicles. in addition, an independent function in membrane fusion has been suggested in vacuolar fusion in yeast and synaptic vesicle exocytosis in fly neurons. evidence for a direct role in secretion has also recently been presented in mouse and worm. the molecular mechanisms of how the v(0) components might act or are regulated are largely unknown. here we report the identification and characterization of a calmod ...200817933871
sequence-dependent variations associated with h2a/h2b depletion of nucleosomes.mechanisms that can alter nucleosome structure to enhance dna accessibility are of great interest because of their potential involvement in genomic processes. one such mechanism is h2a/h2b release from nucleosomes; it occurs in vivo and is involved in the in vitro activities of several transcription-associated complexes. using fluorescence approaches based on förster resonance energy transfer, we previously detected sequence-dependent structure/stability variations between 5s and two types of pr ...200817933873
2-hydroxyphenacyl azoles and related azolium derivatives as antifungal agents.2-hydroxyphenacyl azole and 2-hydroxyphenacyl azolium compounds have been described as a new class of azole antifungals. most target compounds showed significant in vitro antifungal activities against tested fungi (candida albicans, saccharomyces cerevisiae, aspergillus niger, and microsporum gypseum) with low mics values included in the range of 0.25-32 microg/ml comparable to reference drug fluconazole. the most active compounds were also assessed for their cytotoxicity using mtt colorimetric ...200818032039
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
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
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 ...200819161420
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 ...200818982060
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 ...200918990696
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 ...200918992740
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 ...200919684085
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 ...200919707301
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 ...200919726651
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 ...200919732768
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 ...200919755175
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 ...200919188447
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 ...200919193709
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 ...200919197151
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 ...200919200013
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 ...200919209703
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 ...200919211835
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 ...200919225051
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 ...200919229138
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 ...200919233263
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 ...200919252852
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 ...200919254779
triosephosphate isomerase deficiency: new insights into an enigmatic disease.the triosephosphate isomerase (tpi) functions at a metabolic cross-road ensuring the rapid equilibration of the triosephosphates produced by aldolase in glycolysis, which is interconnected to lipid metabolism, to glycerol-3-phosphate shuttle and to the pentose phosphate pathway. the enzyme is a stable homodimer, which is catalytically active only in its dimeric form. tpi deficiency is an autosomal recessive multisystem genetic disease coupled with hemolytic anemia and neurological disorder frequ ...200919786097
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 ...200919794495
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 ...200919815509
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 ...200919834534
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 ...200919915560
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 ...200919915593
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 ...200919933856
[inhibitory effect of dexamethasone on myeloid differentiation factor 88 and tumor necrosis factor-alpha expressions in mouse peritoneal macrophages].to study the inhibitory effect of dexamethasone (dex) on myeloid differentiation factor 88 (myd88) and tumor necrosis factor-alpha (tnf-alpha) expression in mouse peritoneal macrophages in innate immune response to penicillium marneffei (pm).200920034887
full-field transmission x-ray microscopy for bio-imaging.a full-field hard-x-ray microscope at ssrl has successfully imaged samples of biological and environmental origin at 40 nm resolution. phase contrast imaging of trabeculae from a female mouse tibia, loaded in vivo to study the effects of weight-bearing on bone structure, revealed a complex network of osteocytes and canaliculi. imaging of cordgrass roots exposed to mercury revealed nanoparticles with strong absorption contrast. 3d tomography of yeast cells grown in selenium rich media showed inte ...200920111669
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 ...200919948482
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 ...200919942139
mouse neutrophil extracellular traps in microbial infections.neutrophil extracellular traps (nets) play an important role in innate immunity to microbial infections. nets have been described in several species, but the molecular details of net formation and their role in infection has not been addressed, partly because we lack optimal experimental models. here we describe tools to investigate net formation in neutrophils isolated from mice. upon in vitro stimulation of wild-type mouse neutrophils with pma, we analyzed 3 important steps in the process of n ...200920375576
actin and phosphoinositide recruitment to fully formed candida albicans phagosomes in mouse macrophages.candida albicans is a dimorphic yeast that enters macrophages (mphi) via the beta-glucan receptor dectin-1. phagocytosis of c. albicans is characterized by actin polymerization, syk kinase activation and rapid acquisition of phagolysosomal markers. in mice, c. albicans are able to resist the harsh environment of the phagosome and form pseudohyphae inside the phagolysosomal compartment, eventually extending from the mphi. in this study, we investigated these unique c. albicans phagosomes and foun ...200920375582
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 ...200919264152
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 ...200919265539
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 ...200919270744
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 ...200919276668
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 ...200919285746
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 ...200919320974
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 ...200919333396
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 ...200919372138
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 ...200919379832
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 ...200919404540
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 ...200919406113
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 ...200919412885
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 ...200919417210
the new yeast is a mouse! 200919419243
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 ...200919419870
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.200919420685
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.200919422699
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 ...200919427509
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 ...200919433915
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 ...200919450643
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 ...200919452197
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.200919454027
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 ...200919463063
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 ...200919470615
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 ...200919474147
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 ...200919477917
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 ...200919478015
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 ...200919495999
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 ...200919507279
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 ...200919509280
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 ...200919553991
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 ...200919554567
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 ...200919557165
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 ...200919643733
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 ...200919095771
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 ...200919096764
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 ...200919124461
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 ...200919133230
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 ...200919148549
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 ...200919150360
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 ...200919158662
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 ...200919159343
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 ...200919073604
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 ...200919028678
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 ...200919033398
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.200919033885
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 ...200918974045
characterization of scamc-3-like/slc25a41, a novel calcium-independent mitochondrial atp-mg/pi carrier.the scamcs (small calcium-binding mitochondrial carriers) constitute a subfamily of mitochondrial carriers responsible for the atp-mg/p(i) exchange with at least three paralogues in vertebrates. scamc members are proteins with two functional domains, the c-terminal transporter domain and the n-terminal domain which harbours calcium-binding ef-hands and faces the intermembrane space. in the present study, we have characterized a shortened fourth paralogue, scamc-3l (scamc-3-like; also named slc25 ...200918928449
multiple isoforms of beta-trcp display differential activities in the regulation of wnt signaling.the f-box proteins beta-trcp1 and 2 (beta-transducin repeat containing protein) have 2 and 3 isoforms, respectively, due to alternative splicing of exons encoding the n-terminal region. we identified an extra exon in between the previously known exons 1 and 2 of beta-trcp1 and beta-trcp2. interestingly, sequence analysis suggested that many more isoforms are produced than previously identified, via the alternative splicing of all possible combination of exons ii to v of beta-trcp1 and exons ii t ...200918929646
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 ...200918838617
Refresh
firstprev
...212223
nextlast
Displaying items 2001 - 2100 of 2282