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regulation of endocytosis of activin type ii receptors by a novel pdz protein through ral/ral-binding protein 1-dependent pathway.using yeast two-hybrid screening, we have identified a mouse postsynaptic density 95/discs large/zona occludens-1 (pdz) protein that interacts with activin type ii receptors (actriis). we named the protein activin receptor-interacting protein 2 (arip2). arip2 was found to have one pdz domain in the nh(2)-terminal region and interact specifically with actriis among the receptors for the transforming growth factor beta family by the pdz domain. interestingly, overexpression of arip2 enhances endoc ...200211882656
a 320-kilobase artificial chromosome encoding the human hla dr3-dq2 mhc haplotype confers hla restriction in transgenic mice.mhc class ii haplotypes control the specificity of th immune responses and susceptibility to many autoimmune diseases. understanding the role of hla class ii haplotypes in immunity is hampered by the lack of animal models expressing these genes as authentic cis-haplotypes. in this study we describe transgenic expression of the autoimmune prone hla dr3-dq2 haplotype from a yeast artificial chromosome (yac) containing an intact similar320-kb region from hla dra to dqb2. in yac-transgenic mice hla ...200211884478
glutaredoxins and oxidative stress defense in yeast. 200211885267
roles of nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements. 200211885271
characterization of a novel gene adjacent to pax6, revealing synteny conservation with functional significance.the human eye anomaly aniridia is normally caused by intragenic mutations of pax6. several cases of aniridia are, however, associated with chromosomal rearrangements that leave the pax6 gene intact. we have identified and characterized a novel gene, paxneb (c11orf19), downstream (telomeric) of pax6. sequence analysis, including interspecies comparisons, show this gene to consist of 10 exons, with an unusually large final intron spanning 134 kb in human and 18 kb in fugu. this intron is disrupted ...200211889558
murine apg12p has a substrate preference for murine apg7p over three apg8p homologs.apg7p is a unique e1 enzyme which is essential for both the apg12p- and apg8p-modification systems, and plays indispensable roles in yeast autophagy. a cdna encoding murine apg7p homolog (mapg7p) was isolated from a mouse brain cdna library. the predicted amino acid sequence of the clone shows a significant homology to human apg7p and yeast apg7p. murine apg12p as well as the three mammalian apg8p homologs co-immunoprecipitate with mapg7p. site-directed mutagenesis revealed that an active-site c ...200211890701
mrna expression profiling of laser microbeam microdissected cells from slender embryonic structures.microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. the combination of laser microdissection, rna amplification, and microarray hybridization has the potential to provide exp ...200211891179
the pdz proteins pick1, grip, and syntenin bind multiple glutamate receptor subtypes. analysis of pdz binding motifs.using sequence homology searches, yeast two-hybrid assays and glutathione s-transferase (gst)-pull-down approaches we have identified a series of glutamate receptor subunits that interact differentially with the pdz proteins grip, pick1, and syntenin. gst-pull-down experiments identified more interactions than detected by yeast two-hybrid assays. we report several receptor-protein interactions, strong ones include: (i) grip and syntenin with mglur7a, mglur4a, and mglur6; (ii) pick1 and grip with ...200211891216
nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation.the nuclear receptor corepressor (ncor) was isolated as a peroxisome-proliferator-activated receptor (ppar) delta interacting protein using the yeast two-hybrid system. ncor interacted strongly with the ligand-binding domain of ppar delta, whereas interactions with the ligand-binding domains of ppar gamma and ppar alpha were significantly weaker. ppar-ncor interactions were antagonized by ligands in the two-hybrid system, but were ligand-insensitive in in vitro pull-down assays. interaction betw ...200211903058
molecular cloning and sequence analysis of full-length cdnas encoding new group of cyn d 1 isoallergens.cyn d 1, the major allergen of bermuda grass pollen, contains some acidic/basic isoforms. the n-terminal amino acid sequences of some acidic cyn d 1 isoforms were found to be different from those of cyn d 1 cdna clones identified previously.200211906335
identification and characterization of two genes encoding the eukaryotic initiation factor 4a in rice.a cdna encoding eukaryotic translation initiation factor 4a (eif4a) was isolated from a cdna library of rice (oryza sativa l.). based on this dna sequence, a 414-amino acid protein exhibiting 67, 64 and 59% homology to the mouse, schizosaccharomyces pombe and saccharomyces cerevisiae eif4a, respectively, was predicted. the deduced amino acid sequence contains the characteristic motifs shared by the dead box supergene family. another cdna of rice eif4a was reported previously. comparison of the c ...200111913775
liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells.a yeast two-hybrid assay was employed to identify androgen receptor (ar) protein partners in gonadotropin-releasing hormone neuronal cells. by using an ar deletion construct (ar-(delta371-485)) as a bait, beta-catenin was identified as an ar-interacting protein from a gonadotropin-releasing hormone neuronal cell library. immunolocalization of co-transfected ar and flag-beta-catenin demonstrated that flag-beta-catenin was predominantly cytoplasmic in the absence of androgen. in the presence of 5a ...200211916967
defective prelamin a processing and muscular and adipocyte alterations in zmpste24 metalloproteinase-deficient mice.the mouse ortholog of human face-1, zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. disruption of the gene zmpste24 caused severe growth retardation and premature death in homozygous-null mice. histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. t ...200211923874
functional analysis of a vacuolar abc transporter in wild-type candida albicans reveals its involvement in virulence.atp-driven transport proteins belonging to the atp-binding cassette (abc) superfamily perform important functions in cell metabolism and detoxification. compounds can be actively transported across membranes, including the plasma membrane or organellar membranes. the vacuole is an important organelle in fungal cells required for compartmentalization of metabolites as well as toxic substances. sequestration into the vacuole is often energy-dependent. we present the first isolation and molecular a ...200211929516
the phosphorylation status of nuclear nf-kappa b determines its association with cbp/p300 or hdac-1.homodimers of the nf-kappa b p50 subunit are transcriptionally repressive in cells, whereas they can promote transcription in vitro, suggesting that their endogenous effects are mediated by association with other factors. we now demonstrate that transcriptionally inactive nuclear nf-kappab in resting cells consists of homodimers of either p65 or p50 complexed with the histone deacetylase hdac-1. only the p50-hdac-1 complexes bind to dna and suppress nf-kappa b-dependent gene expression in unstim ...200211931769
analysis of the human hephaestin gene and protein: comparative modelling of the n-terminus ecto-domain based upon ceruloplasmin.hephaestin was implicated in mammalian iron homeostasis following its identification as the defective gene in murine sex-linked anaemia. it is a member of the family of copper oxidases that includes mammalian ceruloplasmin, factors v and viii, yeast fet3 and fet5 and bacterial ascorbate oxidase. hephaestin is different from ceruloplasmin, a soluble ferroxidase, in having a membrane-spanning region towards the c-terminus. here we report the gene structure, spanning approximately 100 kb, of the hu ...200211932491
a candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocation.ptosis is defined as drooping of the upper eyelid and can impair full visual acuity. it occurs in a number of forms including congenital bilateral isolated ptosis, which may be familial and for which two linkage groups are known on chromosomes 1p32-34.1 and xq24-27.1. we describe the analysis of the chromosome breakpoints in a patient with congenital bilateral isolated ptosis and a de novo balanced translocation 46,xy,t(1;8)(p34.3;q21.12). both breakpoints were localized by fluorescence in situ ...200211935336
identification and characterization of a sphingolipid delta 4-desaturase family.sphingolipids desaturated at the delta4-position are important signaling molecules in many eukaryotic organisms, including mammals. in a bioinformatics approach, we now identified a new family of protein sequences from animals, plants, and fungi and characterized these sequences biochemically by expression in saccharomyces cerevisiae. this resulted in the identification of the enzyme sphingolipid delta4-desaturase (dihydroceramide desaturase) from homo sapiens, mus musculus, drosophila melanogas ...200211937514
the left-right determinant inversin has highly conserved ankyrin repeat and iq domains and interacts with calmodulin.all vertebrates have a left-right body axis with invariant asymmetries of the heart and the positions of the abdominal viscera. major advances have recently been made in defining molecular components of the pathway specifying the vertebrate left-right axis, but our knowledge of the early determinants is extremely limited. in the invmouse the left-right axis is consistently reversed, unlike other vertebrate mutants where randomisation of situs is apparent. the gene disrupted in this mouse encodes ...200211941489
gga proteins associate with golgi membranes through interaction between their ggah domains and adp-ribosylation factors.adp-ribosylation factors (arfs) are a family of small gtpases that are involved in various aspects of membrane trafficking events. these include arf1-arf6, which are divided into three classes on the basis of similarity in the primary structure: class i, arf1-arf3; class ii, arf4 and arf5; and class iii, arf6. previous studies identified a novel family of potential arf effectors, termed gga1-gga3, which interact specifically with gtp-bound arf1 and arf3 and are localized to the trans-golgi netwo ...200211950392
identification of a novel transcription factor, elys, expressed predominantly in mouse foetal haematopoietic tissues.the precise mechanism governing the generation of haematopoietic stem cells still remains to be understood, partly because the molecules required for early haematopoiesis have not fully been identified.200211952839
death effector domain-containing proteins dedd and flame-3 form nuclear complexes with the tfiiic102 subunit of human transcription factor iiic.death effector domain-containing proteins are involved in important cellular processes such as death-receptor induced apoptosis, nf-kappab activation and erk activation. here we report the identification of a novel nuclear ded-containing protein, flame-3. flame-3 shares significant sequence (46.6% identical) and structural homology to another ded-containing protein, dedd. flame-3 interacts with dedd and c-flip (flame-1) but not with the other ded-containing proteins fadd, caspase-8 or caspase-10 ...200211965497
a positive control for the green fluorescent protein-based one-hybrid system.the yeast one-hybrid system (1h-system) is applied to studies of transcription-linked dna-protein interactions under in vivo conditions detected by reporter gene expression. by use of a variant of green fluorescent protein (gfp) as a reporter, the new 1h-system generation represents a time- and work-saving alternative to the established his3/lacz-based form. however, hitherto, a positive control proving the functionality of the system has been missing. we designed a corresponding control vector ...200211969195
ternary complex formation between mads-box transcription factors and the histone fold protein nf-yb.mads-box proteins are transcription factors present in different eukaryotic kingdoms. in contrast to plants, for mammalian and yeast mads-box proteins ternary complex formation with unrelated transcription factors was reported. we show here the first identification of such ternary interaction in plants. a rice seed-specific nf-yb was identified as partner of osmads18 by two-hybrid screening. nf-yb contains a histone fold motif, hfm,(1) and is part of the trimeric ccaat-binding nf-y complex. osma ...200211971906
cytoplasmic peptide:n-glycanase (pngase) in eukaryotic cells: occurrence, primary structure, and potential functions.a cytoplasmic peptide:n-glycanase has been implicated in the proteasomal degradation of newly synthesized misfolded glycoproteins exported from the endoplasmic reticulum. the gene encoding this enzyme (png1p) has been identified in yeast. based on sequence analysis, png1p was classified as a member of the 'transglutaminase-like superfamily' that contains a putative catalytic triad of amino acids (cysteine, histidine, and aspartic acid). more recent studies in yeast indicate that png1p can bind t ...200211978727
yac transgenic mice carrying pathological alleles of the mjd1 locus exhibit a mild and slowly progressive cerebellar deficit.machado-joseph disease (mjd; mim 109150) is a late-onset neurodegenerative disorder caused by the expansion of a polyglutamine tract within the mjd1 gene. we have previously reported the generation of human yeast artificial chromosome (yac) constructs encompassing the mjd1 locus into which expanded (cag)(76) and (cag)(84) repeat motifs have been introduced by homologous recombination. transgenic mice containing pathological alleles with polyglutamine tract lengths of 64, 67, 72, 76 and 84 repeat ...200211978767
structure of apo-phosphatidylinositol transfer protein alpha provides insight into membrane association.phosphatidylinositol transfer protein alpha (pitp alpha) is a ubiquitous and highly conserved protein in multicellular eukaryotes that catalyzes the exchange of phospholipids between membranes in vitro and participates in cellular phospholipid metabolism, signal transduction and vesicular trafficking in vivo. here we report the three-dimensional crystal structure of a phospholipid-free mouse pitp alpha at 2.0 a resolution. the structure reveals an open conformation characterized by a channel run ...200211980708
rgs3 interacts with 14-3-3 via the n-terminal region distinct from the rgs (regulator of g-protein signalling) domain.rgs3 belongs to a family of the regulators of g-protein signalling (rgs), which bind and inhibit the g alpha subunits of heterotrimeric g-proteins via a homologous rgs domain. increasing evidence suggests that rgs proteins can also interact with targets other than g-proteins. employing yeast two-hybrid screening of a cdna library, we identified an interaction between rgs3 and the phosphoserine-binding protein 14-3-3. this interaction was confirmed by in vitro binding and co-immunoprecipitation e ...200211985497
the ef-hand calcium-binding protein calmyrin inhibits the transcriptional and dna-binding activity of pax3.pax3 is a member of the paired class homeodomain family of transcription factors and has been demonstrated to be an early marker in myogenic differentiation. to gain a better understanding of how protein-protein interactions regulate pax3 transcriptional activity, we performed a yeast two-hybrid analysis to identify proteins that interact with pax3. screening of two cdna libraries isolated nine independent clones that contained the complete encoding sequence of the ef-hand calcium-binding protei ...200211997098
characterization and identification of promoter elements in the mouse cox17 gene.cox17p, essential for the assembly of functional cytochrome c oxidase (cco) in saccharomyces cerevisiae, has been believed to deliver copper ions to the mitochondrion for insertion into the enzyme. we have recently isolated an approximately 20 kb genomic fragment of the mouse cox17. reporter assay experiments have shown that most of the promoter activity was restricted to a 0.85 kb fragment flanking the first exon. further intensive deletion and detailed mutation analysis suggested that the mini ...200211997103
human sir2 deacetylates p53 and antagonizes pml/p53-induced cellular senescence.the yeast sir2 protein mediates chromatin silencing through an intrinsic nad-dependent histone deacetylase activity. sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. here, we show that sirt1, the human sir2 homolog, is recruited to the promyelocytic leukemia protein (pml) nuclear bodies of mammalian cells upon overexpression of either pml or oncogenic ras (ha-rasv12). sirt1 binds and deacetylates p53, a component of pml nuclear bo ...200212006491
a gal4-based yeast three-hybrid system for the identification of small molecule-target protein interactions.we report the development of a yeast strain designed for assaying compound-protein interactions through activation of reporter gene expression. activation of lacz expression, driven by the gal4 promoter, has been demonstrated for precedented compound-protein interactions between fk506 and fk506 binding protein 12 (fkbp12) and also between methotrexate (mtx) and dihydrofolate reductase (dhfr). reporter gene expression was completely abrogated in a competitive manner by the presence of excess fk50 ...200212007565
endocrine disrupter bisphenol a induces orphan nuclear receptor nur77 gene expression and steroidogenesis in mouse testicular leydig cells.the orphan nuclear receptor nur77 (nr4a1) is a member of the nuclear receptor superfamily, which plays an important role in the regulation of lh-mediated steroidogenesis in testicular leydig cells. the aim of the current study was to investigate the potential role of bisphenol a (bpa) on orphan nuclear receptor nur77 gene expression and steroidogenesis. northern blot analysis demonstrated that bpa transiently induced nur77 mrna expression, and protein kinase inhibitor h-89 and pd98059 strongly i ...200212021184
a three-megabase yeast artificial chromosome contig spanning the c57bl mouse igh locus.the mouse ig h chain (igh) complex locus is composed of >100 gene segments encoding the variable, diversity, joining, and constant portions of the ab h chain protein. to advance the characterization of this locus and to identify all the v(h) genes, we have isolated the entire region from c57bl/6 and c57bl/10 as a yeast artificial chromosome contig. the mouse igh locus extends approximately three megabases and contains at least 134 v(h) genes classified in 15 partially interspersed families. two ...200212023364
a krüppel-associated box-zinc finger protein, nt2, represses cell-type-specific promoter activity of the alpha 2(xi) collagen gene.type xi collagen is composed of three chains, alpha 1(xi), alpha 2(xi), and alpha 3(xi), and plays a critical role in the formation of cartilage collagen fibrils and in skeletal morphogenesis. it was previously reported that the -530-bp promoter segment of the alpha 2(xi) collagen gene (col11a2) was sufficient for cartilage-specific expression and that a 24-bp sequence from this segment was able to switch promoter activity from neural tissues to cartilage in transgenic mice when this sequence wa ...200212024037
cloning and characterization of a mammalian fatty acyl-coa elongase as a lipogenic enzyme regulated by srebps.the mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. in the process of searching for genes activated by sterol regulatory element-binding protein 1 (srebp-1) by using dna microarray, we identified and characterized a murine cdna clone that is highly similar to a fatty acyl-coa elongase gene family such as cig30, sscs, and yeast elos. studies on the cells overex ...200212032166
genomic organization, transcript variants and comparative analysis of the human nucleoporin 155 (nup155) gene.nucleoporin 155 (nup155) is a major component of the nuclear pore complex (npc) involved in cellular nucleo-cytoplasmic transport. we have acquired the complete sequence and interpreted the genomic organization of the nup155 orthologos from human (homo sapiens) and pufferfish (fugu rubripes), which are approximately 80 and 8 kb in length, respectively. the human gene is ubiquitously expressed in many tissues analyzed and has two major transcript variants, resulted from an alternative usage of th ...200212034489
synergistic activation of the rat laminin gamma1 chain promoter by the gut-enriched kruppel-like factor (gklf/klf4) and sp1.laminin is a multifunctional heterotrimeric protein present in extracellular matrix where it regulates processes that compose tissue architecture including cell differentiation. laminin gamma1 is the most widely expressed laminin chain and its absence causes early lethality in mouse embryos. laminin gamma1 chain gene (lamc1) promoter contains several gc/gt-rich motifs including the bcn-1 element. using the bcn-1 element as a bait in the yeast one-hybrid screen, we cloned the gut-enriched kruppel ...200212034813
identification and characterization of cdnas encoding four novel proteins that interact with translin associated factor-x.translin-associated factor x (trax) is the predominantly cytoplasmic binding partner of tb-rbp/translin in mouse testis. four mouse testis cdnas encoding specific trax-interacting proteins were isolated from a yeast two-hybrid library screen. one novel cdna designated tsnaxip1 (trax-interacting protein-1) encodes 709 amino acids. we isolated a cdna encoding the 427 carboxy-terminal amino acids of mea-2, a golgi-associated, maleenhanced autoantigen; a cdna encoding 429 amino acids with 73% homolo ...200212036294
multiprotein bridging factor-1 (mbf-1) is a cofactor for nuclear receptors that regulate lipid metabolism.multiprotein bridging factor (mbf-1) is a cofactor that was first described for its capacity to modulate the activity of fushi tarazu factor 1, a nuclear receptor originally implicated in drosophila development. recently, it has been shown that human mbf-1 stimulates the transcriptional activity of steroidogenic factor 1, a human homolog of fushi tarazu factor 1, which is implicated in steroidogenesis. here we show that this cofactor enhances the transcriptional activity of several nonsteroid nu ...200212040021
identification, cloning and expression of the mouse n-acetylglutamate synthase gene.in ureotelic animals, n-acetylglutamate (nag) is an essential allosteric activator of carbamylphosphate synthetase i (cpsi), the first enzyme in the urea cycle. nag synthase (nags; ec 2.3.1.1) catalyses the formation of nag from glutamate and acetyl-coa in liver and intestinal mitochondria. this enzyme is supposed to regulate ureagenesis by producing variable amounts of nag, thus modulating cpsi activity. moreover, inherited deficiencies in nags have been associated with hyperammonaemia, probabl ...200212049647
an essential role for rev3 in mammalian cell survival: absence of rev3 induces p53-independent embryonic death.the rev3 gene of budding yeast encodes the catalytic subunit of dna polymerase zeta that carries out translesion dna synthesis. while rev3-null yeast mutants are viable and exhibit normal growth, rev3-deficient mice die around midgestation of embryogenesis, which is accompanied by massive apoptosis of cells within the embryo proper. we have investigated whether rev3 is required for the survival of mouse cells and whether the embryonic lethality caused by rev3 deficiency can be rescued by introdu ...200212051777
degradation of ornithine decarboxylase in saccharomyces cerevisiae is ubiquitin independent.ornithine decarboxylase (odc), the first rate-limiting enzyme in the polyamine biosynthesis is one of the most rapidly degraded proteins in eukaryotic cells. mammalian odc is a notable exception to the widely accepted dogma that ubiquitination is always required for targeting a protein to degradation by the 26s proteasome. however, while it is well established that in mammalian cells degradation of odc is ubiquitin independent, the requirement of ubiquitination for degradation of odc in yeast ce ...200212054575
rat zinc-fingers and homeoboxes 1 (zhx1), a nuclear factor-ya-interacting nuclear protein, forms a homodimer.zinc-fingers and homeoboxes 1 (zhx1) is a protein which interacts with the activation domain of the a subunit of nuclear factor-y. to analyze the physiological role(s) of zhx1, we searched zhx1-interacting protein(s) using a yeast two-hybrid system. the rat counterpart of zhx1 cdnas was cloned from an ovarian granulosa cell complementary dna (cdna) library, indicating that zhx1 is able to form a homodimer. an analysis of the nucleotide sequence and its deduced amino acid sequence show that rat z ...200212062805
implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target-of-rapamycin pathway in prolactin receptor signalling.a prolactin (prl)-responsive 3'-end cdna encoding rat alpha4 phosphoprotein was previously isolated from a rat lymphoma cdna library. rat alpha4 is a homologue of yeast tap42 and is a component of the mammalian target-of-rapamycin (mtor) signalling pathway that stimulates translation initiation and g1 progression in response to nutrients and growth factors. in the present study, the full-length rat alpha4 cdna was obtained by 5'-race and the 1023 bp open reading frame predicted a 340 amino acid ...200212065239
deletion of the copper transporter caccc2 reveals two distinct pathways for iron acquisition in candida albicans.efficient iron acquisition is an essential requirement for growth of pathogenic organisms in the iron-poor host environment. in saccharomyces cerevisiae, high-affinity iron import depends on the multicopper ferroxidase scfet3. scfet3 biogenesis in the trans-golgi compartment requires a copper-transporting p-type atpase, scccc2. here, we describe the isolation by functional complementation of a ccc2 homologue from the pathogenic yeast candida albicans. caccc2 is functionally distinct from a previ ...200212067343
previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis.during spermiogenesis (the maturation of spermatids into spermatozoa) in many vertebrate species, protamines replace histones to become the primary dna-packaging protein. it has long been thought that this process is facilitated by the hyperacetylation of histone h4. however, the responsible histone acetyltransferase enzymes are yet to be identified. cdy is a human y-chromosomal gene family expressed exclusively in the testis and implicated in male infertility. its mouse homolog cdyl, which is a ...200212072557
the molecular mechanism of translocation through the nuclear pore complex is highly conserved.in this report we investigated the activity of vertebrate nuclear transport factors in a primitive organism, amoeba proteus, to better understand evolutionary changes in the transport mechanisms of organisms expected to have different requirements for nucleocytoplasmic exchange. it was initially determined that fxfg-containing nucleoporins and ran, both of which are essential for nuclear import in vertebrates, as well as yeast, are also present and functional in amoebae. this suggests that there ...200212082159
genome-wide binding map of the histone deacetylase rpd3 in yeast.we describe the genome-wide distribution of the histone deacetylase and repressor rpd3 and its associated proteins ume1 and ume6 in saccharomyces cerevisiae. using a new cross-linking protocol, we found that rpd3 binds upstream of many individual genes and upstream of members of gene classes with similar functions in anabolic processes. in addition, rpd3 is preferentially associated with promoters that direct high transcriptional activity. we also found that rpd3 was absent from large sub-telome ...200212089521
ptprj is a candidate for the mouse colon-cancer susceptibility locus scc1 and is frequently deleted in human cancers.only a small proportion of cancers result from familial cancer syndromes with mendelian inheritance. nonfamilial, 'sporadic' cancers, which represent most cancer cases, also have a significant hereditary component, but the genes involved have low penetrance and are extremely difficult to detect. therefore, mapping and cloning of quantitative trait loci (qtls) for cancer susceptibility in animals could help identify homologous genes in humans. several cancer-susceptibility qtls have been mapped i ...200212089527
structure, upstream promoter region, and functional domains of a mouse and human mix paired-like homeobox gene.mix/bix proteins represent a vertebrate subgroup of paired-like homeodomain proteins which are known to function around the time of gastrulation. here we report the structures of the genomic and upstream promoter regions of a mouse and human mix-like gene. both genes map to syntenic regions of chromosome 1 and contain two coding exons, with the paired-type homeodomain split between the exons within helix 3. differentiating mouse embryonic stem cells transcribe a messenger rna of approximately 2. ...200212095687
an endoplasmic reticulum stress-specific caspase cascade in apoptosis. cytochrome c-independent activation of caspase-9 by caspase-12.activation of caspase-12 from procaspase-12 is specifically induced by insult to the endoplasmic reticulum (er) (nakagawa, t., zhu, h., morishima, n., li, e., xu, j., yankner, b. a., and yuan, j. (2000) nature 403, 98-103), yet the functional consequences of caspase-12 activation have been unclear. we have shown that recombinant caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. the activated caspase-9 catalyzes cleavage of procaspase-3, which is inhibitable by a c ...200212097332
sphingosine kinases: a novel family of lipid kinases.sphingosine kinase (sphk) catalyzes the formation of sphingosine-1-phosphate (s11). s1p plays an important role in regulation of a variety of biological processes through intracellular and extracellular actions. s1p has recently been shown to be the ligand for the edg-1 family of g-protein-coupled receptors. to date, seven cloned sphks have been reported with confirmed sphk activity, including human, mouse, yeast, and plant. a computer search of various databases suggests that a new sphk family ...200212102559
sox9 transactivation and testicular expression of a novel human gene, kiaa0800.the sry and sox9 sex-determination factors initiate and promote testis differentiation by gene transactivation through similar promoter elements. however, knowledge is limited concerning what genes are regulated by sry/sox9 in the testis. identification and characterization of sry/sox9-regulated genes are critical for understanding sexual differentiation. we now demonstrate that a novel human gene, kiaa0800, is preferentially expressed in the testis and is transactivated by sox9. the kiaa0800 pr ...200212111997
a major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia.cytogenetic and molecular studies have provided evidence of the clustering of chromosome 2 deletion breakpoints in radiation-induced murine acute myeloid leukemia (aml). moreover, clustering occurs in at least two fragile domains rich in telomere-like arrays. here we describe a physical map of the distal breakpoint cluster and confirm the presence of inverted head-to-head telomeric sequence arrays. these potentially recombinogenic sequences were not, however, the direct focus for post-irradiatio ...200212112312
yes-associated protein (yap65) interacts with smad7 and potentiates its inhibitory activity against tgf-beta/smad signaling.members of the tgf-beta family of growth factors signal from the cell surface through serine/threonine kinase receptors. intracellular propagation of the signal occurs by phosphorylation of intracellular proteins of the smad family. smad7 belongs to the subclass of inhibitory smads that function as antagonists of tgf-beta signaling. a yeast two-hybrid screen of a human placental cdna expression library using full-length mouse smad7 as bait identified yes-associated protein (yap65) as a novel sma ...200212118366
differential localization of the vacuolar h+ pump with g subunit isoforms (g1 and g2) in mouse neurons.vacuolar h(+)-atpases (v-atpases), a family of multimeric proton pumps, are involved in a wide variety of physiological processes. we have identified two mouse genes, atp6g1 and atp6g2, encoding the g1 and g2 isoforms of the v-atpase g subunit, respectively. g1 was distributed ubiquitously in the tissues examined, whereas g2 was specifically distributed in central nervous system neurons. g1 was expressed at an early embryonic stage, whereas g2 transcription was significantly induced at 10.5 days ...200212133826
general statistics of stochastic process of gene expression in eukaryotic cells.thousands of genes are expressed at such very low levels (< or =1 copy per cell) that global gene expression analysis of rarer transcripts remains problematic. ambiguity in identification of rarer transcripts creates considerable uncertainty in fundamental questions such as the total number of genes expressed in an organism and the biological significance of rarer transcripts. knowing the distribution of the true number of genes expressed at each level and the corresponding gene expression level ...200212136033
nath, a novel gene overexpressed in papillary thyroid carcinomas.in this study a replica cdna screening (rcs) approach to identify genes differentially expressed in papillary thyroid carcinomas (ptc) was used, as compared to non-neoplastic thyroid tissues. rcs is based on hybridization of radioactively labeled cdna probes made from the biopsies to replica membranes with 15 000 clones from a ptc cdna library. among the genes overexpressed in ptc, and especially in clinically aggressive tumors with histologic evidence of poorly differentiated or undifferentiate ...200212140756
type xxvi collagen, a new member of the collagen family, is specifically expressed in the testis and ovary.hsp47 is a collagen-specific molecular chaperone that specifically recognizes and binds to the triple helical domain of various types of collagens. here we report the cloning of the entire coding region of a novel collagen-like protein by yeast two-hybrid screening of a 17.5-day whole mouse embryo cdna library using hsp47 as a bait. the cdna of this protein and its deduced amino acid sequence are 2,690 bp and 438 amino acids long, respectively. the protein contains two clusters of gly-x-y collag ...200212145293
unsafe sets: histone lysine methyltransferases and cancer.enzymes that covalently modify histones control many cellular processes by affecting gene expression. a new class of these enzymes is the histone lysine methyltransferase family, whose catalytic activity lies within a conserved domain, the set domain. this article surveys the evidence for a connection between set-domain-containing proteins and cancer. it proposes that deregulation of set-domain function has an important role in carcinogenesis.200212151224
molecular characterization of the pb recombination hotspot in the mouse major histocompatibility complex class ii region.in the mouse major histocompatibility complex (mhc) class ii region, meiotic recombination breakpoints are clustered in four specific sites known as hotspots. here we reveal the primary structure of a hotspot near the pb gene. a total of 12 crossover points were found to be confined to a 15-kb dna segment of the pb pseudogene. moreover, the crossover points are concentrated in a 341-bp segment, which includes a part of exon 4 and intron 4 of the pb gene. all four mhc hotspots appear to be locate ...200212160737
viral interferon regulatory factor 1 of kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, grim19, and inhibits interferon/retinoic acid-induced cell death.kaposi's sarcoma-associated herpesvirus (kshv) plays a significant role in the development of kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric castleman's disease. the kshv open reading frame k9 encodes the viral interferon (ifn) factor 1 (virf1), which downregulates ifn- and irf-mediated transcriptional activation, and leads to cellular transformation in rodent fibroblasts and induction of tumors in nude mice. using the yeast two-hybrid assay, we identified genes asso ...200212163600
mcm3-binding ganp dna-primase is associated with a novel phosphatase component g5pr.ganp, carrying dna-primase and mcm3-binding domains, is up-regulated in germinal centre b cells. to understand the regulatory function of ganp upon mcm complex, we searched for ganp-associated molecules by yeast two-hybrid screening.200212167160
the multiple lim domain-containing adaptor protein hic-5 synaptically colocalizes and interacts with the dopamine transporter.the na+/cl--dependent dopamine transporter (dat) is critical in terminating dopaminergic transmission by removing the transmitter away from the synapse. several lines of evidence suggest that transporter-interacting proteins may play a role in dat function and regulation. in this report, using the yeast two-hybrid system, we have identified a novel interaction between dat and the multiple lin-11, isl-1, and mec-3 (lim) domain-containing adaptor protein hic-5. this association involves the n-term ...200212177201
negative regulation of epstein-barr virus latent membrane protein 1-mediated functions by the bone morphogenetic protein receptor ia-binding protein, bram1.the latent membrane protein 1 (lmp1) of epstein-barr virus causes cellular transformation and activates several intracellular signals, including nf-kappab and c-jun n-terminal kinase. using yeast two-hybrid screening with the lmp1 c-terminal sequence as bait, we demonstrate that bram1 (bone morphogenetic protein receptor-associated molecule 1) is an lmp1-interacting protein. bram1 associates with lmp1, both in vitro and in vivo, as revealed by confocal microscopy, glutathione s-transferase pull- ...200212181323
d2 and d3 dopamine receptor cell surface localization mediated by interaction with protein 4.1n.we identified protein 4.1n as a d2-like dopamine receptor-interacting protein in a yeast two-hybrid screen. protein 4.1n is a neuronally enriched member of the 4.1 family of cytoskeletal proteins, which also includes protein 4.1r of erythrocytes and the 4.1g and 4.1b isoforms. the interaction of protein 4.1n was specific for the d2 and d3 dopamine receptors and was independently confirmed in pulldown and coimmunoprecipitation assays. deletion mapping localized the site of dopamine receptor/prote ...200212181426
microtubule-dependent subcellular redistribution of the transcriptional coactivator p/cip.the transcriptional coactivator p/cip is a member of a family of nuclear receptor coactivator/steroid receptor coactivator (ncoa/src) proteins that mediate the transcriptional activities of nuclear hormone receptors. we have found that p/cip is predominantly cytoplasmic in a large proportion of cells in various tissues of the developing mouse and in a number of established cell lines. in mouse embryonic fibroblasts, serum deprivation results in the redistribution of p/cip to the cytoplasmic comp ...200212192059
the sumo ubiquitin-protein isopeptide ligase family member miz1/piasxbeta /siz2 is a transcriptional cofactor for tfii-i.we have shown previously that a tfii-i-related protein, hmustrd1/ben, represses transcriptional activity of tfii-i. the repression by hmustrd1/ben was hypothesized to occur via a two-step competition mechanism involving a cytoplasmic shuttling factor and a nuclear cofactor required for transcriptional activation of tfii-i. employing a two-hybrid approach with both yeast genomic and mouse cdna libraries in parallel, we have identified the ring-like zinc finger containing miz1/piasxbeta/siz2, whic ...200212193603
timing of apc/c substrate degradation is determined by fzy/fzr specificity of destruction boxes.the anaphase promoting complex/cyclosome (apc/c), activated by fzy and fzr, degrades cell cycle proteins that carry rxxl or ken destruction boxes (d-boxes). apc/c substrates regulate sequential events and must be degraded in the correct order during mitosis and g(1). we studied how d-boxes determine apc/c(fzy)/apc/c(fzr) specificity and degradation timing. cyclin b1 has an rxxl box and is degraded by both apc/c(fzy) and apc/c(fzr); fzy has a ken box and is degraded by apc/c(fzr) only. we charact ...200212198152
tis7 interacts with the mammalian sin3 histone deacetylase complex in epithelial cells.the mammalian sin3 complex consists of histone deacetylases (hdac1, hdac2), several known proteins (sap30, n-cor) and as yet unidentified proteins. here we show that the mouse tetradecanoyl phorbol acetate induced sequence 7 (tis7) protein is a novel transcriptional co-repressor that can associate with the sin3 complex. we have identified tis7 as a gene that is up-regulated upon loss of polarity in a mouse mammary gland epithelial cell line expressing an estrogen-inducible c-juner fusion protein ...200212198164
cpap is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity.stat5, a member of the signal transducer and activators of transcription (stat) protein family, is a primary mediator of prolactin (prl) signaling in the mammary gland. there are two distinct stat5 genes, stat5a and stat5b. the stat5a isoform has been demonstrated to have an essential role in mammary epithelial differentiation, whereas stat5b is required for dimorphic sexual growth. to search for proteins that interact with the c terminus of stat5a, a highly divergent region amongst stat family ...200212198240
cloning and characterization of gripe, a novel interacting partner of the transcription factor e12 in developing mouse forebrain.the helix-loop-helix (hlh) family of transcription factors are key contributors to a wide array of developmental processes, including neurogenesis and hematopoiesis. these factors are thought to exert their regulatory influences by binding to cognate promoter-dna sequences as dimers. although studies in mice have convincingly demonstrated that neurogenic hlh proteins such as neurod are intimately involved in neuronal fate determination, the role of the ubiquitously expressed hlh protein, e12, in ...200212200424
identification of ribosomal proteins specific to higher eukaryotic organisms.this report describes the identification of a novel protein named ps1d (genbank accession number ), which is composed of an s1-like rna-binding domain, a (cysteine)x3-(histidine) ccch-zinc finger, and a very basic carboxyl domain. ps1d is expressed as two isoforms, probably resulting from the alternative splicing of mrna. the long ps1d isoform differs from the short one by the presence of 48 additional amino acids at its amino-terminal extremity. analysis of ps1d subcellular distribution by cell ...200212202495
kif1bbeta2, capable of interacting with chp, is localized to synaptic vesicles.kinesin family proteins are microtubule-dependent molecular motors involved in the intracellular motile process. using a ca2+ -binding protein, chp (calcineurin b homologous protein), as a bait for yeast two hybrid screening, we identified a novel kinesin-related protein, kif1bbeta2. kif1bbeta2 is a member of the kif1 subfamily of kinesin-related proteins, and consists of an amino terminal kif1b-type motor domain followed by a tail region highly similar to that of kif1a. chp binds to regions adj ...200212204119
structural conservation between the actin monomer-binding sites of twinfilin and actin-depolymerizing factor (adf)/cofilin.twinfilin is an evolutionarily conserved actin monomer-binding protein that regulates cytoskeletal dynamics in organisms from yeast to mammals. it is composed of two actin-depolymerization factor homology (adf-h) domains that show approximately 20% sequence identity to adf/cofilin proteins. in contrast to adf/cofilins, which bind both g-actin and f-actin and promote filament depolymerization, twinfilin interacts only with g-actin. to elucidate the molecular mechanisms of twinfilin-actin monomer ...200212207032
treasures and traps in genome-wide data sets: case examples from yeast.since the publication of the saccharomyces cerevisiae genome sequence, much effort has been dedicated to developing high-throughput techniques to generate comprehensive information about the function and dynamics of all genes in this yeast's genome. these techniques have generated data sets that typically contain large amounts of reliable and valuable biological information. nevertheless, there are also uncertainties that are associated with such large-scale studies, which we discuss in this rev ...200212209140
glucose down-regulates per1 and per2 mrna levels and induces circadian gene expression in cultured rat-1 fibroblasts.in mammals, peripheral circadian clocks are present in most tissues, but little is known about how these clocks are synchronized with the ambient 24-h cycles. by using rat-1 fibroblasts, a model cell system of the peripheral clock, we found that an exchange of the culture medium triggered circadian gene expression that was preceded by slow down-regulation of per1 and per2 mrna levels. this profile contrasts to the immediate up-regulation of these genes often observed for clock resetting. the scr ...200212213820
sumo-1 modification of the c-terminal kvekvd of axin is required for jnk activation but has no effect on wnt signaling.axin is a multifunctional protein, regulating wnt signaling and the c-jun n-terminal/stress-activated protein kinase (jnk/sapk) pathway as well as tumorigenesis. in the present study, we found that axin interacts with three sumo-1 (small ubiquitin-related modifier) conjugating enzymes 3 (e3), pias1, piasxbeta, and piasy. the extreme c-terminal six amino acid residues of axin are critical for the axin/e3 interaction as deletion of the six residues (axindeltac6) completely abolished the ability of ...200212223491
candida-specific antibodies during experimental vaginal candidiasis in mice.protective host defense mechanisms against vaginal candida albicans infections are poorly understood. although cell-mediated immunity (cmi) is the predominant host defense mechanism against most mucosal candida infections, the role of cmi against vaginal candidiasis is uncertain, both in humans and in an experimental mouse model. the role of humoral immunity is equally unclear. while clinical observations suggest a minimal role for antibodies against vaginal candidiasis, an experimental rat mode ...200212228309
giardia lamblia: identification and characterization of rab and gdi proteins in a genome survey of the er to golgi endomembrane system.to investigate the complexity of the endomembrane transport system in the early diverging eukaryote, giardia lamblia, we characterized homologues of the gtp-binding proteins, rab1 and rab2, involved in regulating vesicular trafficking between the endoplasmic reticulum and golgi in higher eukaryotes, and gdi, which plays a key role in the cycling of rab proteins. g. lamblia rab1, 2.1, and gdi sequences largely resemble yeast and mammalian homologues, are transcribed as 0.66-, 0.62-, and 1.4-kb me ...200212243734
ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities.the mechanisms of pathology for the family of polyglutamine disease proteins are unknown; however, recently it was shown that several of these proteins inhibit transcription suggesting that transcriptional repression may be a potential mechanism for pathology. in the present study we use cell transfections, in vitro binding, co-immunoprecipitations, and reporter assays to show that the polyglutamine disease protein, ataxin-3, interacts with the major histone acetyltransferases camp-response-elem ...200212297501
trafficking of the vesicular acetylcholine transporter in sn56 cells: a dynamin-sensitive step and interaction with the ap-2 adaptor complex.the pathways by which synaptic vesicle proteins reach their destination are not completely defined. here we investigated the traffic of a green fluorescent protein (gfp)-tagged version of the vesicular acetylcholine transporter (vacht) in cholinergic sn56 cells, a model system for neuronal processing of this cargo. gfp-vacht accumulates in small vesicular compartments in varicosities, but perturbation of endocytosis with a dominant negative mutant of dynamin i-k44a impaired gfp-vacht trafficking ...200212358769
analysis of o-acetyl-adp-ribose as a target for nudix adp-ribose hydrolases.the sir2 family of nad(+)-dependent histone/protein deacetylases has been implicated in a wide range of biological activities, including gene silencing, life span extension, and chromosomal stability. recent evidence has indicated that these proteins produce a novel metabolite o-acetyl-adp-ribose (oaadpr) during deacetylation. cellular studies have demonstrated that this metabolite exhibits biological effects when microinjected in living cells. however, the molecular targets of oaadpr remain to ...200212370179
sharp is a novel component of the notch/rbp-jkappa signalling pathway.notch proteins are the receptors for an evolutionarily highly conserved signalling pathway that regulates numerous cell fate decisions during development. signal transduction involves the presenilin-dependent intracellular processing of notch and nuclear translocation of the intracellular domain of notch, notch-ic. notch-ic associates with the dna-binding protein rbp-jkappa/cbf-1 to activate transcription of notch target genes. in the absence of notch signalling, rbp-jkappa/cbf-1 acts as a trans ...200212374742
the inherited blindness associated protein aipl1 interacts with the cell cycle regulator protein nub1.mutations in the aryl hydrocarbon receptor-interacting protein-like 1 (aipl1) gene have been found in patients with leber congenital amaurosis (lca), a severe, early-onset form of retinal degeneration. to determine the normal function of aipl1 and to better understand how mutations in this gene cause disease, we performed a yeast two-hybrid screen to identify aipl1-interacting proteins in the retina. one of the identified interacting proteins corresponds to nub1 (nedd8 ultimate buster 1), which ...200212374762
a novel brain-expressed protein related to carnitine palmitoyltransferase i.malonyl-coenzymea acts as a fuel sensor, being both an intermediate of fatty acid synthesis and an inhibitor of the two known isoforms of carnitine palmitoyltransferase i (cpt i), which control mitochondrial fatty acid oxidation. we describe here a novel cpt1 family member whose mrna is present predominantly in brain and testis. chromosomal locations and genome organization are reported for the mouse and human genes. the protein sequence contains all the residues known to be important for both c ...200212376098
an evolutionarily conserved fission yeast protein, ned1, implicated in normal nuclear morphology and chromosome stability, interacts with dis3, pim1/rcc1 and an essential nucleoporin.we identified a novel fission yeast gene, ned1(+), with pleiotropic mutations that have a high incidence of chromosome missegregation, aberrantly shaped nuclei, overdeveloped endoplasmic reticulum-like membranes, and increased sensitivity to a microtubule destabilizing agent. ned1 protein, which was phosphorylated in a growth-related manner, interacted in a yeast two-hybrid system with dis3 as well as with pim1/rcc1 (nucleotide exchange factor for ran). ned1 also interacted with an essential nuc ...200212376568
regulation of egr-1 by association with the proteasome component c8.primary response transcription factor, egr-1, is rapidly activated by a variety of extracellular stimuli. activation of egr-1 is shown to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. egr-1 is a short-lived protein, but the mechanism that regulates its stability has not yet been clarified. in this study, the yeast two-hybrid screening revealed that egr-1 interacts significantly with prc8 ...200212379479
cation chloride cotransporters interact with the stress-related kinases ste20-related proline-alanine-rich kinase (spak) and oxidative stress response 1 (osr1).cells respond to stress stimuli by mounting specific responses. during osmotic and oxidative stress, cation chloride cotransporters, e.g. na-k-2cl and k-cl cotransporters, are activated to maintain fluid/ion homeostasis. here we report the interaction of the stress-related serine-threonine kinases ste20-related proline-alanine-rich kinase (spak) and oxidative stress response 1 (osr1) with the cotransporters kcc3, nkcc1, and nkcc2 but not kcc1 and kcc4. the interaction was identified using yeast ...200212386165
molecular cloning of a gene for inversion of embryo turning (inv) with cystic kidney.vertebrate internal organs of the body develop with a distinctive left-right asymmetry. the mouse inversion of embryonic turning (inv) mutation which was created by random insertional mutagenesis causes a constant reversal of the left-right polarity (situs inversus) as well as cyst formation in the kidney in homozygotes. since this phenotype is tightly linked to the transgenic integration site, the disrupted gene is likely to be located near this site. to analyse the transgenic integration site, ...200212386294
genetic analysis of sorting nexins 1 and 2 reveals a redundant and essential function in mice.sorting nexins 1 (snx1) and 2 (snx2) are homologues of the yeast gene vps5 that is required for proper endosome-to-golgi trafficking. the prevailing thought is that vps5p is a component of a retrograde trafficking complex called the retromer. genetic and biochemical evidence suggest mammals may have similar complexes, but their biological role is unknown. furthermore, if snx1 and snx2 belong to such complexes, it is not known whether they act together or separately. herein, we show that mice lac ...200212388759
activating signal cointegrator 1 is highly expressed in murine testicular leydig cells and enhances the ligand-dependent transactivation of androgen receptor.activating signal cointegrator 1 (asc-1) has been recently reported as a coactivator of some nuclear receptors. in the present study, we have analyzed the expression of asc-1 in the mouse testis and investigated its capacity to modulate the transcriptional activity of androgen receptor (ar). we found that although asc-1 mrna was ubiquitously expressed at a low level in mouse tissues, a couple of testis-specific mrnas were expressed in the adult testis. cloning of one testis-specific variant reve ...200212390891
retroviral vectors for establishing tetracycline-regulated gene expression in an otherwise recalcitrant cell line.tetracycline-regulated systems have been used to control the expression of heterologous genes in such diverse organisms as yeast, plants, flies and mice. adaptation of this prokaryotic regulatory system avoids many of the problems inherent in other inducible systems. there have, however, been many reports of difficulties in establishing functioning stable cell lines due to the cytotoxic effects of expressing high levels of the tetracycline transactivator, tta, from a strong viral promoter.200212392602
hip14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis.huntington disease (hd) is caused by polyglutamine [poly(q)] expansion in the protein huntingtin (htt). although the exact mechanism of disease progression remains to be elucidated, altered interactions of mutant htt with its protein partners could contribute to the disease. using the yeast two-hybrid system, we have isolated a novel htt interacting protein, hip14. hip14's interaction with htt is inversely correlated to the poly(q) length in htt. mrnas of 9 and 6 bp are transcribed from the hip1 ...200212393793
cell surface expression of a gpi-anchored form of mouse acetylcholinesterase in klpmr1delta cells of kluyveromyces lactis.the mouse acetylcholinesterase ache(h) was expressed in the yeast kluyveromyces lactis. the ache(h) activity was detectable in intact cells whereas it was absent in the culture media. glucanase treatment and immunoelectron microscopy data indicated that ache(h) is anchored to plasma membrane and that the mouse gpi-signaling is compatible with the k. lactis targeting machinery. the ache(h) was also expressed in a k. lactis strain carrying an inactivated allele of klpmr1, the gene coding for a p-t ...200212408988
inactivation of kex2p diminishes the virulence of candida albicans.deletion of the kexin gene (kex2) in candida albicans has a pleiotropic effect on phenotype and virulence due partly to a defect in the expression of two major virulence factors: the secretion of active aspartyl proteinases and the formation of hyphae. kex2/kex2 mutants are highly attenuated in a mouse systemic infection model and persist within cultured macrophages for at least 24 h without causing damage. pathology is modest, with little disruption of kidney matrix. the infecting mutant cells ...200312419804
production of interleukin-1 activity of kupffer cells from mice treated with the acidic mannan fraction of baker's yeast.we investigated the production of interleukin-1 (il-1) activity by kupffer cells (kc) from mice treated with a neutral mannan fraction (wnm) or an acidic mannan fraction (wam025) from baker's yeast (saccharomyces cerevisiae) in vivo and in vitro. the mice administered wam025 showed an increase in the number of kc and the il-1 production compared with mice administered wnm. in an in vitro stimulation assay using kc from a normal mouse, it was also found that wam025 displayed an increase in il-1 p ...200212419972
a novel germ line-specific gene of the phosducin-like protein (phlp) family. a meiotic function conserved from yeast to mice.we identified a new member of the phosducin-like (phlp) protein family that is predominantly, if not exclusively, expressed in male and female germ cells. in situ analysis on testis sections and analysis of purified spermatogenic cell fractions evidenced a stage-specific expression with high levels of rna and protein in pachytene spermatocytes and round spermatids. three mrna species were detected, which correspond to different polyadenylation sites and vary in abundance during germ cell maturat ...200312424248
identification of a nipsnap homologue as host cell target for salmonella virulence protein spic.salmonella enterica uses a type iii secretion system encoded by spi-2 to target specific virulence factors into the host cytosol of macrophages to inhibit the phagosomal-lysosomal maturation pathway. this ensures survival of salmonella inside its intracellular niche, the salmonella-containing vacuole (scv). one such virulence factor is spic, which was previously shown to interfere with intracellular vesicular trafficking. in this study we have used a yeast two-hybrid assay to identify a nipsnap ...200212427096
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