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molecular cloning and expression of a cdna encoding a protein tyrosine phosphatase from mouse brain.a mouse brain cdna library was screened with a radioisotope-labeled probe of human placental protein tyrosine phosphatase. the isolated clone (mbptp1b) was found to contain an open reading frame of 1,296 nucleotides as well as 5' (709 nucleotides) and 3' (341 nucleotides) non-coding regions. this cdna encodes a ptp of 432 amino acids having a mass of 49,563 daltons and exhibiting 83% and 93.5% sequence identity to that of human ptp1b and rat ptp1, respectively. the expression of the cdna in yeas ...19968955893
a novel serine/threonine kinase gene, gek1, is expressed in meiotic testicular germ cells and primordial germ cells.we have isolated a novel serine/ threonine kinase gene designated gek1 from mouse primordial germ cell-derived embryonic germ cell. gek1 is preferentially expressed in meiotic testicular germ cells and primordial germ cells. gek1 mrna is also detected in several other tissues, including hematopoietic organs in adult mice and central nervous system in embryos. the gek1 cdna encodes a protein with the consensus sequence of the catalytic domain of protein kinases in its n-terminal region. the deduc ...19968956278
human huntingtin derived from yac transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype.huntington disease (hd) is caused by expansion of a cag trinucleotide repeat in exon 1 of a novel gene. the hd protein (huntingtin) plays a critical role in early embryonic development since homozygous targeted disruption of the murine hd gene results in embryonic lethality by day 7.5. to rescue this phenotype by transgene based huntingtin expression it is therefore essential to express the protein early enough in development in the appropriate cells. since yac based transgenes are known to be r ...19968968738
removal of an intron with unique 3' branch site creates an amino-terminal protein sequence directing the scerv1 gene product to mitochondria.the yeast scerv1 gene is of special interest because it has a dual function in mitochondrial biogenesis and in the regulation of the cell cycle. the recent discovery that the yeast scerv1 gene has a structural and functional human homologue initiated a detailed comparison of the genes and their structures. in addition the homologous alr (augmenter of liver regeneration) genes from rat and mouse have just been identified and it has been found that the mammalian proteins have a specific function i ...19968972573
refined mapping of the usher syndrome type iii locus on chromosome 3, exclusion of candidate genes, and identification of the putative mouse homologous region.a locus for usher syndrome type iii (ush3; mim no. 276902) was recently assigned to a 5-cm region on chromosome 3q. we constructed a yeast artificial chromosome contig that allowed us to position novel polymorphisms in the region. these were typed in a total of 32 pedigrees from a geographically isolated finnish founder population in which a putative single ancestral ush3 mutation segregates. a multipoint linkage analysis assigned ush3 to a 4-cm region between d3s1555 and a novel marker d3s3625. ...19968975700
cloning, expression pattern and mapping to xq of nap1l3, a gene encoding a peptide homologous to human and yeast nucleosome assembly proteins.from a human fetal brain cdna library, we isolated a novel gene sharing significant homology with the genes of nucleosome assembly proteins (naps). this cdna clone, designated nap1l3 (nucleosome assembly protein 1-like 3), contained an open reading frame of 1518 nucleotides encoding 506 amino acids. its predicted amino acid sequence showed 46% identity and 65% similarity with nap1l. in its c-terminal half nap1l3 contained several characteristic motifs strictly conserved with nap1l and yeast nap1 ...19968976385
expression of the meiosis-specific synaptonemal complex protein 1 in a heterologous system results in the formation of large protein structures.the synaptonemal complex is a meiosis-specific structure essential for synapsis of homologous chromosomes. the synaptonemal complex protein 1 (scp1) is a major constituent of the transversal filament, a fibrous structure that connects the central element of the synaptonemal complex with the two lateral elements. the scp1 protein forms filamentous dimers with the two molecules that have the same polarity, with the c-termini being anchored in the lateral elements and the n-termini reaching into th ...19968986609
cdp1, a novel saccharomyces cerevisiae gene required for proper nuclear division and chromosome segregation.to identify new gene products involved in chromosome segregation, we isolated saccharomyces cerevisiae mutants that require centromere binding factor i (cbf1p) for viability. one cbf1p-dependent mutant (denoted cdp1-1) was selected for further analysis. the cdp1 gene encodes a novel 125-kd protein that is notably similar to previously identified mouse, human and caenorhabditis elegans proteins. cdp1 delta and cdp1-1 mutant cells were temperature sensitive for growth. at the permissive temperatur ...19968978028
a possible involvement of tif1 alpha and tif1 beta in the epigenetic control of transcription by nuclear receptors.nuclear receptors (nrs) are ligand-inducible transcription factors that mediate complex effects on development, differentiation and homeostasis. they regulate the transcription of their target genes through binding to cognate dna sequences as homodimers or heterodimers. the molecular mechanisms underlying transcriptional activation by nrs are still poorly understood, although intermediary factors (mediators) appear to be involved in mediating the transactivation functions of nrs. tif1 has been i ...19968978696
insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and dead eye, essential for embryonic development.recently our laboratory described an efficient method for generating retroviral provirus insertions in the zebrafish germ line, and we showed that provirus insertions induce embryonic mutations at a frequency of roughly one mutant per 70 insertions. to date we have isolated four insertional mutants and, using the proviruses as a molecular tag, have cloned the genes disrupted in three of them. the proviruses in all three mutants lie within or just 5' of the first coding exon, point in the opposit ...19968985183
a novel member of the ring finger family, krip-1, associates with the krab-a transcriptional repressor domain of zinc finger proteins.the krüppel-associated box a (krab-a) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the cys2-his2 type. using the yeast two-hybrid system, we report the isolation of a cdna encoding a novel murine protein, krab-a interacting protein 1 (krip-1) that physically interacts with the krab-a region. krip-1 is a member of the rbcc subfamily of the ring finger, or cys3hiscys4, family of zinc binding proteins whose othe ...19968986806
functional promoter elements common to ribosomal protein and ribosomal rna genes in neurospora crassa.the promoter sequences of a cytoplasmic ribosomal protein gene (crp-2) of neurospora crassa were identified using promoter deletion and substitution mutants. a gene-targeting strategy was used to assay the mutants in vivo. the promoter architecture of crp-2 is complex and is more similar to that of ribosomal protein genes in mouse than in saccharomyces cerevisiae. six regions were identified as important for transcription. these included two elements, a cg repeat and a dde box, that are conserve ...19969003305
dna repair functions in heterologous cells.our genetic information is constantly challenged by exposure to endogenous and exogenous dna-damaging agents, by dna polymerase errors, and thereby inherent instability of the dna molecule itself. the integrity of our genetic information is maintained by numerous dna repair pathways, and the importance of these pathways is underscored by their remarkable structural and functional conservation across the evolutionary spectrum. because of the highly conserved nature of dna repair, the enzymes invo ...19968994804
complementary dna cloning and sequencing of the chicken muscle ecto-atpase. homology with the lymphoid cell activation antigen cd39.the ecto-atpase from chicken gizzard (smooth muscle) was solubilized, and the 66-kda cell membrane ecto-atpase protein was purified. the protein was then subjected to both enzymatic and chemical cleavage, and the resultant peptides were purified by reverse phase high pressure liquid chromatography and sequenced. several of these internal peptide sequences were used to design oligonucleotides to screen a chicken muscle library to identify the cdna encoding the ecto-atpase. two overlapping partial ...19978995405
molecular cloning of the papillary renal cell carcinoma-associated translocation (x;1)(p11;q21) breakpoint.a combination of southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization techniques was used to map yacs, cosmids and dna markers from the xp11.2 region relative to the x chromosome breakpoint of the renal cell carcinoma-associated t(x;1)(p11;q21). the position of the breakpoint could be determined as follows: xcen-oatl2-dxs146-dxs255-syp-t(x;1)-tfe 3-oatl1-xpter. fluorescence in situ hybridization experiments using tfe3-containing yacs and ...19968995477
cloning and expression of a novel gene for a protein with leucine-rich repeats in the developing mouse nervous system.in a variety of organisms from yeast to humans, members of the leucine-rich repeat (lrr) family, in which one repeal consists of 24 amino acids and leucine residues appear regularly, have been shown to be involved in protein-protein interactions. in drosophila, members of this family have significant functions in neural development. it is thus possible that similar molecules play a crucial role in the morphogenesis of the mammalian nervous system. using a human brain cdna fragment encoding an lr ...19969011764
a mutation in the xpb/ercc3 dna repair transcription gene, associated with trichothiodystrophy.trichothiodystrophy (ttd) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is associated with ttd. virtually all photosensitive ttd patients have a deficiency in the nucleotide excision repair (ner) of uv-induced dna damage that is indistinguishable from that of xeroderma pigmentosum (xp) complem ...19979012405
structure and expression of the mouse casein gene locus.the analysis of yeast artificial chromosomes (yacs) containing the complete mouse casein gene locus revealed the presence of five casein genes, alpha-, beta-, gamma-, delta-, and kappa-casein, in this order, in the locus. the alpha- and beta-casein genes are only 10 kb apart and have convergent transcriptional orientations. the distance between the beta-casein gene and the alpha s2-like gamma-casein gene is about 70 kb, and these genes have divergent transcriptional orientations. the gamma- and ...19979021141
the multiple murine 3 beta-hydroxysteroid dehydrogenase isoforms: structure, function, and tissue- and developmentally specific expression.the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-hsd) is essential for the biosynthesis of all active steroid hormones. to date five distinct isoforms have been identified in the mouse. the different isoforms are indicated by roman numerals (i-v) in the chronological order in which they have been isolated. the different isoforms are expressed in a tissue- and developmentally specific manner and fall into two functionally distinct groups. 3 beta-hsd i, ii, and iii function as nad(+)-depende ...19979029733
incubation at the nonpermissive temperature induces deficiencies in uv resistance and mutagenesis in mouse mutant cells expressing a temperature-sensitive ubiquitin-activating enzyme (e1).in temperature-sensitive (ts) mutants of mouse fm3a cells, the levels of mutagenesis and survival of cells treated with dna-damaging agents have been difficult to assess because they are killed after their mutant phenotypes are expressed at the nonpermissive temperature. to avoid this difficulty, we incubated the ts mutant cells at the restrictive temperature, 39 degrees c, for only a limited period after inducing dna damage. we used ts mutants defective in genes for ubiquitin-activating enzyme ...19979032276
mitochondrial dna polymerases from yeast to man: a new family of polymerases.we report the sequence of a 4.5-kb cdna clone isolated from a human melanoma library which bears high amino acid sequence identity to the yeast mitochondrial (mt) dna polymerase (mip1p). this cdna contains a 3720-bp open reading frame encoding a predicted 140-kda polypeptide that is 43% identical to mip1p. the n-terminal part of the sequence contains a 13 glutamine stretch encoded by a cag trinucleotide repeat which is not found in the other dna polymerases gamma (pol gamma). multiple amino acid ...19979034326
investigation of growth hormone releasing hormone receptor structure and activity using yeast expression technologies.growth hormone releasing hormone (ghrh) is the positive regulator of growth hormone synthesis and secretion in the anterior pituitary. the peptide confers activity by binding to a seven transmembrane domain g protein-coupled receptor. signal transduction proceeds through subsequent g alpha s stimulation of adenylyl cyclase. to investigate ligand/receptor and receptor/g protein associations, the human ghrh receptor was expressed in a modified s. cerevisiae strain which allows for facile measureme ...19979029497
lethal effect of recombinant human fas ligand in mice pretreated with propionibacterium acnes.fas ligand (fasl) is a type ii membrane protein. binding of fasl to its receptor, fas, induces apoptosis. matrix metalloproteinase cleaves the membrane-bound human fasl to yield the active soluble form. here, we have produced a large amount of human soluble rfasl using the yeast, pichia pastoris. the purified rfasl was found to be glycosylated and to exist as a trimer. the rfasl was effective in inducing apoptosis in a fas-expressing t cell or a fibroblast cell line. the id50 of rfasl for mouse ...19979036978
identification of interaction partners for the basic-helix-loop-helix protein e47.helix-loop-helix proteins constitute a family of transcription factors with the potential to form homo- and hetero-dimers mediated by the helix-loop-helix domain. oncogenic mutations in such genes can disrupt the equilibrium of protein-protein interactions in the affected cell. in order to assess the biological consequences of such mutations, the full complement of interacting proteins must be known. to identify proteins interacting with the basic-helix-loop-helix domain of the ubiquitously expr ...19979050988
characterization of two age-induced intracisternal a-particle-related transcripts in the mouse liver. transcriptional read-through into an open reading frame with similarities to the yeast ccr4 transcription factor.intracisternal a-particle (iap) sequences are endogenous retrovirus-like elements present at 1,000 copies in the mouse genome. we had previously identified iap-related transcripts of unusual size (6 and 10 kilobases (kb)), which are observed exclusively in the liver of the aging mouse. in this report, using cdna libraries that we have constructed from the liver mrnas of an aged dba/2 mouse, we have cloned and entirely sequenced the corresponding cdnas. both are initiated within the 5' long termi ...19979038221
cloning and identification of mouse steroid receptor coactivator-1 (msrc-1), as a coactivator of peroxisome proliferator-activated receptor gamma.peroxisome proliferator-activated receptor gamma (ppargamma), a member of the nuclear receptor superfamily, is expressed predominantly in adipose tissue. forced expression of the two isoforms of this receptor, ppargamma1 and ppargamma2, in fibroblasts initiates a transcriptional cascade that leads to the development of adipocyte phenotype. using the yeast two-hybrid system and gal4-ppargamma as bait to screen mouse liver cdna library, we isolated a mouse steroid receptor coactivator (msrc-1) inv ...19969041124
crf2-4: isolation of cdna clones encoding the human and mouse proteins.to search for genes which encode human interferon receptor molecules, we applied the technique of exon trapping to human chromosome 21 yeast artificial chromosomes (yacs). a full length cdna encoding human crf2-4 was identified which is shown here to be widely expressed in human tissues. the human crf2-4 cdna was used as a probe to screen a mouse macrophage cdna library. a mouse crf2-4 cdna was isolated which encodes a 349-amino-acid (aa) polypeptide that is 69% identical at the aa level with it ...19979047351
dbl family proteins. 19979061011
ufd1l, a developmentally expressed ubiquitination gene, is deleted in catch 22 syndrome.the catch 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in digeorge (dgs) and velo-cardio-facial (vcfs) syndromes. hemizygosity of this region may also be the cause of over 100 different clinical signs. the catch 22 locus maps within a 1.5 mb region, which encompasses several genes. however, no single defect in 22q11.2 hemizygous patients can be ascribed to any gene so far is ...19979063746
cloning and characterization of hupf1, a human homolog of the saccharomyces cerevisiae nonsense mrna-reducing upf1 protein.levels of most nonsense mrnas are normally reduced in prokaryotes and eukaryotes when compared with that of corresponding functional mrnas. genes encoding polypeptides that selectively reduce levels of nonsense mrna have so far only been identified in simple eukaryotes. we have now cloned a human cdna whose deduced amino acid sequence shows the highest degree of homology to that of upf1, a bona fide saccharomyces cerevisiae group i rna helicase required for accelerated degradation of nonsense mr ...19979064659
proviral integrations at the evi5 locus disrupt a novel 90 kda protein with homology to the tre2 oncogene and cell-cycle regulatory proteins.evi5 is a common site of retroviral integration in t-cell lymphomas of akxd mice. mapping studies have localized evi5 to a region approximately 18 kb upstream of another common viral integration site, gfi1, on mouse chromosome 5 (liao x, jenkins na and copeland ng, (1995a). j. virol., 69, 7132-7137). gfi1 encodes a zinc finger transcription factor involved in interleukin-2 signaling. to determine if evi5 encodes a gene separate from gfi1 that might also be involved in t-cell disease, we have sea ...19979070650
the s3a ribosomal protein gene is identical to the fte-1 (v-fos transformation effector) gene and the tnf-alpha-induced tu-11 gene, and its transcript level is altered in transformed and tumor cells.previous work on mouse x rat hybrid cells (bs series) led to the assignment of a transformation suppressor locus (sail) to the rat 5q22-q33 region. this gene is not yet identified. from a non-transformed bs hybrid cell line, we isolated a partial cdna insert (13t), which detects a transcript more abundant in transformed cells than in their non-transformed homologs. sequence comparisons led us to conclude that 13t is identical to the coding sequences of the ribosomal protein s3a gene (rps3a), of ...19979074506
estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, mcf-7 human breast cancer cells, and yeast-based estrogen receptor assays: no apparent synergism.the estrogenic activity of dieldrin, toxaphene, and an equimolar mixture of both compounds (dieldrin/toxaphene) was investigated in the 21-day-old b6c3f1 mouse uterus, mcf-7 human breast cancer cells, and in yeast-based reporter gene assays. treatment of the animals with 17beta-estradiol (e2) (0.0053 kg/day x3) resulted in a 3.1-, 4.8-, and 7.8-fold increase in uterine wet weight, peroxidase activity, and progesterone receptor binding, respectively. in contrast, treatment with 2.5, 15 and 60 mic ...19979075711
isolation and characterization of cdna encoding mouse rna polymerase ii subunit rpb14.by means of the yeast two-hybrid system using the 40-kda subunit of mouse rna polymerase i, mrpa40, as the bait, we isolated a mouse cdna which encoded a protein with significant homology in amino acid sequence to the 12.5-kda subunit of saccharomyces cerevisiae rna polymerase ii, b12.5 (rpb11). specific antibody raised against the recombinant protein that was derived from the cdna reacted with a 14-kda polypeptide in highly purified mammalian rna polymerase ii and did not react with any subunit ...19979099876
functional analysis of the fission yeast prp4 protein kinase involved in pre-mrna splicing and isolation of a putative mammalian homologue.the prp4 gene of schizosaccharomyces pombe encodes a protein kinase. a physiological substrate is not yet known. a mutational analysis of prp4 revealed that the protein consists of a short n-terminal domain, containing several essential motifs, which is followed by the kinase catalytic domain comprising the c-terminus of the protein. overexpression of n-terminal mutations disturbs mitosis and produces elongated cells, using a pcr approach, we isolated a putative homologue of prp4 from human and ...19979102632
molecular cloning of mouse liver flavin containing monooxygenase (fmo1) cdna and characterization of the expression product: metabolism of the neurotoxin, 1,2,3,4-tetrahydroisoquinoline (tiq).a mouse liver cdna clone, mfmo1, coding for a flavin-containing monooxygenase (fmo) was isolated. this cdna clone encoded a protein of 532 amino acids. based upon its predicted amino acid sequence, this clone was assumed to belong to the fmo1 subfamily. the deduced amino acid sequence showed 94, 84, 83, and 83% identity with fmo1s of rats, pigs, rabbits and humans, respectively, while it showed only 50-59% identity with human fmo3 and fmo4, rabbit fmo2, fmo3, fmo4 and fmo5, and guinea-pig fmo2. ...19979076656
the molecular interaction of fas and fap-1. a tripeptide blocker of human fas interaction with fap-1 promotes fas-induced apoptosis.fas (apo-1/cd95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. a protein tyrosine phosphatase, fas-associated phosphatase-1 (fap-1), that was previously identified as a fas binding protein interacts with the c-terminal 15 amino acids of the regulatory domain of the fas receptor. to identify the minimal region of the fas c-terminal necessary for binding to fap-1, we employed an in vitro inhibition assay of fas/fap-1 bindin ...19979079683
molecular evolution of cytochrome c oxidase subunit iv: evidence for positive selection in simian primates.cytochrome c oxidase (cox) is a multi-subunit enzyme complex that catalyzes the final step of electron transfer through the respiratory chain on the mitochondrial inner membrane. up to 13 subunits encoded by both the mitochondrial (subunits i, ii, and iii) and nuclear genomes occur in eukaryotic organisms ranging from yeast to human. previously, we observed a high number of amino acid replacements in the human cox iv subunit compared to mouse, rat, and cow orthologues. here we examined cox iv ev ...19979115172
regulation of the myeloid-cell-expressed human gp91-phox gene as studied by transfer of yeast artificial chromosome clones into embryonic stem cells: suppression of a variegated cellular pattern of expression requires a full complement of distant cis elements.identifying the full repertoire of cis elements required for gene expression in mammalian cells (or animals) is challenging, given the moderate sizes of many loci. to study how the human gp91-phox gene is expressed specifically in myeloid hematopoietic cells, we introduced yeast artificial chromosome (yac) clones and derivatives generated in yeast into mouse embryonic stem cells competent to differentiate to myeloid cells in vitro or into mouse chimeras. fully appropriate regulation was recapitu ...19979121478
harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins bcl-2 and bcl-x(l).programmed cell death is essential in organ development and tissue homeostasis and its deregulation is associated with the development of several diseases in mice and humans. the precise mechanisms that control cell death have not been elucidated fully, but it is well established that this form of cellular demise is regulated by a genetic program which is activated in the dying cell. here we report the identification, cloning and characterization of harakiri, a novel gene that regulates apoptosi ...19979130713
stat5 is a physiological substrate of the insulin receptor.using the cytoplasmic domain of the insulin receptor (ir) in a yeast two-hybrid screen, we identified a cdna clone encoding the c-terminal 308 amino acids of human stat5b (stat5b-ct). stat5b-ct is tyrosine phosphorylated by purified ir kinase domain in vitro. insulin stimulates tyrosine phosphorylation of overexpressed stat5b-ct and endogenous stat5 in cells overexpressing ir. stat5 may be a direct target of the ir and, as a member of the stat family of transcription factors, may play a role in ...19979122188
binary transgenic mouse model for studying the trans control of globin gene switching: evidence that gata-1 is an in vivo repressor of human epsilon gene expression.to test whether human gata-1 (hgata-1) is involved in the transcriptional control of globin gene switching, we produced transgenic mice overexpressing hgata-1, crossed them with mice carrying a human beta-globin locus yeast artificial chromosome (beta yac), and analyzed globin gene expression in their progeny. mice carrying both the hgata-1 and the beta yac transgenes had normal levels of gamma- and beta-globin mrna and no distortion in the rate or in the timing of gamma-to-beta switch, indicati ...19979122214
hip-i: a huntingtin interacting protein isolated by the yeast two-hybrid system.we report the discovery of the huntingtin interacting protein i (hip-i) which binds specifically to the n-terminus of human huntingtin, both in the two-hybrid screen and in in vitro binding experiments. for the interaction in vivo, a protein region downstream of the polyglutamine stretch in huntingtin is essential. the hip1 cdna isolated by the two-hybrid screen encodes a 55 kda fragment of a novel protein. using an affinity-purified polyclonal antibody raised against recombinant hip-i, a protei ...19979147654
a membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection.in recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). such discordant xenografts, however, are subject to hyperacute rejection (har) and activation of host complement plays a major role in this rejection. this problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement.19969135084
functional expression of the murine golgi cmp-sialic acid transporter in saccharomyces cerevisiae.we have functionally expressed the murine golgi putative cmp-sialic acid transporter in saccharomyces cerevisiae. using a galactose-inducible expression system, s. cerevisiae vesicles were able to transport cmp-sialic acid. transport was dependent on galactose induction and was temperature-dependent and saturable with an apparent km of 2.9 microm. transport was inhibited by cmp, and upon vesicle disruption with triton x-100 parameters were very similar to the previously described cmp-sialic acid ...19979139716
estrogen receptor residues required for stereospecific ligand recognition and activation.the mouse estrogen receptor (mer) has been shown to exhibit stereospecific binding of certain stilbene estrogen agonists. the region of the mer involved in the stereochemical recognition of ligands was further defined using a stilbene isomer, indenestrol b (ib). the ib compound has a chiral carbon bearing an ethyl substituent, and the wild type uterine mer has been shown to bind the enantiomers, ib-s and ib-r, with similar affinity. the wild type mer expressed in yeast exhibited a very minor pre ...19979139802
isolation of a full-length human wnt7a gene implicated in limb development and cell transformation, and mapping to chromosome 3p25.the wnt gene family has a role in development as well as tumourigenesis. one mouse member, wnt7a, is vital for limb development in vivo and also possesses transforming ability in vitro. this study reports the isolation of a full length of human homologue of mouse wnt7a gene by library screening. yeast artificial chromosome-fluorescence in situ hybridisation (yac-fish) mapped the wnt7a gene to chromosome 3p25. human wnt7a had an orf encoding a deduced protein of 349 aa that exhibited 97% and 92% ...19979161407
repression by ume6 involves recruitment of a complex containing sin3 corepressor and rpd3 histone deacetylase to target promoters.sin3 and rpd3 negatively regulate a diverse set of yeast genes. a mouse sin3-related protein is a transcriptional corepressor, and a human rpd3 homolog is a histone deacetylase. here, we show that sin3 and rpd3 are specifically required for transcriptional repression by ume6, a dna-binding protein that regulates genes involved in meiosis. a short region of ume6 is sufficient to repress transcription, and this repression domain mediates a two-hybrid and physical interaction with sin3. coimmunopre ...19979150136
cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, aik, related to aurora of drosophila and yeast ipl1.mutations in aurora of drosophila and related saccharomyces cerevisiae ipl1 kinase are known to cause abnormal chromosome segregation. we have isolated a cdna encoding a novel human protein kinase of 402 amino acids with a predicted molecular mass of 45.9 kda, which shares high amino acid identities with the aurora/ipl1 protein kinase family; hence the cdna is designated as aik (aurora/ipl1-related kinase). amino acid sequence of c-terminal kinase domain of aik shares 86, 86, 72, 59, and 49% ide ...19979153231
the xpb subunit of repair/transcription factor tfiih directly interacts with sug1, a subunit of the 26s proteasome and putative transcription factor.mutations in the basal transcription initiation/dna repair factor tfiih are responsible for three human disorders: xeroderma pigmentosum (xp), cockayne syndrome (cs) and trichothiodystrophy (ttd). the non-repair features of cs and ttd are thought to be due to a partial inactivation of the transcription function of the complex. to search for proteins whose interaction with tfiih subunits is disturbed by mutations in patients we used the yeast two-hybrid system and report the isolation of a novel ...19979173976
yarrowia lipolytica srp54 homolog and translocation of kar2p.to investigate the role of srp54p in protein translocation, the yarrowia lipolytica srp54 homolog was cloned. sequencing revealed an open reading frame of 536 amino acids coding for a 57.2 kilodalton polypeptide with 55 to 57% sequence identity to srp54ps of saccharomyces cerevisiae, schizosaccharomyces pombe, and mouse. like these srp54ps, y. lipolytica srp54p has an n-terminal domain with a highly conserved gtp-binding site and a methionine-rich c-terminal domain. differing results regarding t ...19979178502
tolerance of low ph in schizosaccharomyces pombe requires a functioning pub1 ubiquitin ligase.a strain of schizosaccharomyces pombe carrying a disrupted na+/h+ antiporter gene (sod2::sup3-5), in addition to the common auxotrophic mutations, ade6-216, ura4-d18 and leu1-32, is highly sensitive to media adjusted to ph 6.9. reversion analysis of this strain yielded a group of revertants capable of growth at ph 6.9. two of the revertants elongated and failed to form colonies at ph 3.5. genetic characterization of one of the ph-sensitive elongated strains, j227, showed the presence of two inde ...19979197411
a new family of 10 murine ovalbumin serpins includes two homologs of proteinase inhibitor 8 and two homologs of the granzyme b inhibitor (proteinase inhibitor 9).serine proteinase inhibitors (serpins) are classically regulators of extracellular proteolysis, however, recent evidence suggests that some function intracellularly. such "ovalbumin" serpins include the human proteinase inhibitors 6 (pi-6), 8 (pi-8), and 9 (pi-9), plasminogen activator inhibitor 2, and the monocyte/neutrophil elastase inhibitor. pi-9 is a potent granzyme b (grab) inhibitor that has an unusual p1 glu and is present primarily in lymphocytes. in a search for the murine equivalent o ...19979182575
a truncated form of rgs3 negatively regulates g protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase c.identification of a new family of proteins (rgs proteins) that function as negative regulators of g protein signaling has sparked new understanding of desensitization of this signaling process. recent studies with several mammalian rgs proteins has delineated their ability to interact with and function as gtpase-activating proteins specifically for g proteins in the gi family. here, we investigated the functional activity of rgs3 and a truncated form of rgs3 on g protein-coupled receptor-mediate ...19979182581
cell surface expression of two major yeast allergens in the pityrosporum genus.we have previously identified two major allergens of pityrosporum orbiculare and characterized these as 37 kda and 67 kda proteins.19979179435
nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures.the mouse nedd5 gene encodes a 41.5-kd gtpase similar to the saccharomyces and drosophila septins essential for cytokinesis. nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. microinjection of anti-nedd5 antibody interferes with cytokinesis, giving rise to binucleated cells. in interphase and postmitotic cells, nedd5 localizes to fibrous or granular structures depending on the growth state of the cell. the nedd5-containing fibers ...19979203580
p140mdia, a mammalian homolog of drosophila diaphanous, is a target protein for rho small gtpase and is a ligand for profilin.rho small gtpase regulates cell morphology, adhesion and cytokinesis through the actin cytoskeleton. we have identified a protein, p140mdia, as a downstream effector of rho. it is a mammalian homolog of drosophila diaphanous, a protein required for cytokinesis, and belongs to a family of formin-related proteins containing repetitive polyproline stretches. p140mdia binds selectively to the gtp-bound form of rho and also binds to profilin. p140mdia, profilin and rhoa are co-localized in the spread ...19979214622
transposon-generated 'knock-out' and 'knock-in' gene-targeting constructs for use in mice.the conventional technique for targeted mutation of mouse genes entails placing a genomic dna fragment containing the gene of interest into a vector for fine mapping, followed by cloning of two genomic arms around a selectable neomycin-resistance cassette in a vector containing thymidine kinase [1]; this generally requires 1-2 months of work for each construct. the single 'knock-out' construct is then transfected into mouse embryonic stem (es) cells, which are subsequently subjected to positive ...19979210379
murine model of niemann-pick c disease: mutation in a cholesterol homeostasis gene.an integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of niemann-pick type c (np-c) disease. the predicted murine npc1 protein has sequence homology to the putative transmembrane domains of the hedgehog signaling molecule patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme a (hmg-coa) reductase and srebp cleavage-activating protein (scap), and to the npc1 orthologs identified i ...19979211850
effect of transcriptional regulatory sequences on autonomous replication of plasmids in transient mammalian systems.transcriptional regulatory sequences often influence the efficiency of dna replication, directly or indirectly, in bacteria, yeast, and animal virus systems. we have tested several transcriptional regulatory sequences for affecting dna replication, based on puc vector, in transient systems. autonomous replication of transfected plasmids was assayed by pcr amplification of the fragments derived from the plasmids, which had replicated in mammalian cells. by this highly efficient method of detectin ...19979212977
direct involvement of the ubiquitin-conjugating enzyme ubc9/hus5 in the degradation of ikappabalpha.the nf-kappab/rel proteins are sequestered in the cytoplasm in association with ikappabalpha. in response to external signals, ikappabalpha is phosphorylated, multi-ubiquitinated, and degraded by proteasomes, thereby releasing nf-kappab/rel proteins to migrate to the nucleus. we have cloned a mouse ubiquitin-conjugating enzyme (me2), which associates with ikappabalpha. me2 is homologous to the yeast ubc9/hus5 ubiquitin-conjugating enzyme. a transdominant-negative mutant of me2 had no effect on p ...19979223278
cr3-dependent phagocytosis by murine macrophages: different cytokines regulate ingestion of a defined cr3 ligand and complement-opsonized cryptococcus neoformans.phagocytosis is a fundamental process in innate resistance to infection. we have used the pathogenic yeast cryptococcus neoformans to study the interaction of this encapsulated organism with murine macrophages in vitro. in the absence of exogenous opsonins the encapsulated yeast is almost totally resistant to ingestion by murine macrophages. owing to its ability to activate the alternative complement pathway, the anti-phagocytic properties of the polysaccharide capsule can be partially overcome ...19979227330
establishment of a novel host, high-red yeast that stably expresses hamster nadph-cytochrome p450 oxidoreductase: usefulness for examination of the function of mammalian cytochrome p450.a novel strain of saccharomyces cerevisiae useful for expression studies of mammalian microsomal cytochrome p450s was established and named high-red yeast. hamster nadph-cytochrome p450 oxidoreductase (p450 reductase) cdna to be introduced into yeast was isolated from a hamster liver cdna library. the cdna was 2421 bp long and contained an entire coding region for 667 amino acids. the nh2-terminal amino acid sequence deduced from the hamster p450 reductase cdna was identical with that of the enz ...19979224733
atp-binding properties of human hsp90.hsp90 is one of the most abundant proteins in the cytosol of eukaryotic cells. under physiological conditions hsp90 has been shown to play a major role in several specific signaling pathways, including maturation of various kinases and maintenance of steroid receptors in an activable state. it is well established that the level of hsp90 increases severalfold under stress conditions, and it has been shown that the chaperone function of hsp90 is atp-independent. although yeast hsp90 does not bind ...19979228028
zeb, a vertebrate homolog of drosophila zfh-1, is a negative regulator of muscle differentiation.a number of genes, spanning the evolutionary scale from yeast to mammals, that are involved in spatial and temporal patterning during development contain zinc finger and homeodomain motifs. one such zinc finger/homeodomain protein is drosophila zfh-1, a member of the zfh family of drosophila genes, which is expressed in muscle precursors and is critical for the proper development of muscle. here we demonstrate that a vertebrate homolog of zfh-1 (zeb) is a negative regulator of muscle differentia ...19979233803
cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-coa synthetase mrna decrease.the effects of sodium cholate on high-fat diet-induced hyperglycemia and obesity were investigated. insulin resistance was estimated by measuring 2-deoxyglucose uptake in epitrochlearis muscles incubated in vitro. addition of 0.5% cholate to high-safflower oil diet completely prevented high fat-induced hyperglycemia and obesity in c57bl/6j mice with a slight decrease of energy intake but with no inhibition of fat absorption. furthermore, the addition of cholate decreased blood insulin levels and ...19979252477
interaction of ctla-4 with ap50, a clathrin-coated pit adaptor protein.ctla-4 plays a critical role in regulating the immune response. it is mainly located in cytoplasmic vesicles and is expressed only transiently on the surface after t cell activation. in this study, we demonstrate that ctla-4 is associated with ap50, the medium chain of the clathrin-associated coated pit adaptor protein complex ap2. in a yeast two-hybrid screen, three individual cdna clones that encode mouse ap50 were isolated, all of which can interact specifically with the cytoplasmic domain of ...19979256472
identification of a new mammalian centrin gene, more closely related to saccharomyces cerevisiae cdc31 gene.among the numerous centrin isoforms identified by two-dimensional gel electrophoresis in human cells, an acidic and slow-migrating isoform is particularly enriched in a centrosome fraction. we report here that this isoform specifically reacts with antibodies raised against saccharomyces cerevisiae cdc31p and is present, as other centrin isoforms, in the distal lumen of centrioles. it is encoded by a new centrin gene, which we propose to name hscen3 (homo sapiens centrin gene 3). this gene is mor ...19979256449
a novel murine p-450 gene, cyp4a14, is part of a cluster of cyp4a and cyp4b, but not of cyp4f, genes in mouse and humans.genomic clones for cyp4a12 and a novel member of the murine cyp4a gene family were isolated. the novel gene, designated cyp4a14, has a gc rich sequence immediately 5' of the transcription start site, and is similar to the rat cyp4a2 and cyp4a3 genes. the cyp4a14 gene spans approximately 13 kb, and contains 12 exons; sequence similarity to the rat cyp4a2 gene sequence falls off 300 bp upstream from the start site. in view of the known sex-specific expression of the rat cyp4a2 gene, the expression ...19979271096
isolation of a mouse cdna encoding msti1, a stress-inducible protein containing the tpr motif.we report the isolation and sequencing of the complete 2079-bp cdna fragment encoding msti1, a murine stress-inducible protein. the predicted orf encodes a protein of 543 amino acids (aa) and mr 62,582. the predicted protein has significant homology to stress-inducible proteins from humans (ief ssp 3521), soybean (gmsti), yeast (sti1) and a parasite, leishmania donovani (lsip). all of these proteins contain 34-aa repeat motifs, termed tetratricopeptide repeats (tprs), that are proposed to be inv ...19979272871
localization of a domain in the fimh adhesin of escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection.the fimh subunit of type 1-fimbriated escherichia coli has been implicated as an important determinant of bacterial adherence and colonization of the urinary tract. here, we sought to localize the functionally important domain(s) within the fimh molecule and to determine if antibodies against this domain would block adherence of type 1-fimbriated e. coli to the bladder mucosa in situ and in vivo in an established mouse model of cystitis. we generated translational fusion proteins of disparate re ...19979276729
genetic and physical mapping of the mouse host resistance locus lgn1. 19979271671
clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic t-cell leukaemia.ataxia-telangiectasia (a-t) is a recessive multi-system disorder caused by mutations in the atm gene at 11q22-q23 (ref. 3). the risk of cancer, especially lymphoid neoplasias, is substantially elevated in a-t patients and has long been associated with chromosomal instability. by analysing tumour dna from patients with sporadic t-cell prolymphocytic leukaemia (t-pll), a rare clonal malignancy with similarities to a mature t-cell leukaemia seen in a-t, we demonstrate a high frequency of atm mutati ...19979288106
evaluation of a recombinant yeast cell estrogen screening assay.a wide range of chemicals with diverse structures derived from plant and environmental origins are reported to have hormonal activity. the potential for appreciable exposure of humans to such substances prompts the need to develop sensitive screening methods to quantitate and evaluate the risk to the public. yeast cells transformed with plasmids encoding the human estrogen receptor and an estrogen responsive promoter linked to a reporter gene were evaluated for screening compounds for estrogenic ...19979294720
nonfilamentous c. albicans mutants are avirulent.candida albicans and saccharomyces cerevisiae switch from a yeast to a filamentous form. in saccharomyces, this switch is controlled by two regulatory proteins, ste12p and phd1p. single-mutant strains, ste12/ste12 or phd1/phd1, are partially defective, whereas the ste12/ste12 phd1/phd1 double mutant is completely defective in filamentous growth and is noninvasive. the equivalent cph1/cph1 efg1/efg1 double mutant in candida (cph1p is the ste12p homolog and efg1p is the phd1p homolog) is also defe ...19979298905
smad4 and fast-1 in the assembly of activin-responsive factor.members of the tgf-beta superfamily of signalling molecules work by activating transmembrane receptors with phosphorylating activity (serine-threonine kinase receptors); these in turn phosphorylate and activate smads, a class of signal transducers. activins are growth factors that act primarily through smad2, possibly in partnership with smad4, which forms heteromeric complexes with different ligand-specific smads after activation. in frog embryos, smad2 participates in an activin-responsive fac ...19979288972
cdna cloning and expression of murine 1-acyl-sn-glycerol-3-phosphate acyltransferase.1-acyl-sn-glycerol-3-phosphate (1-agp), also known as lysophosphatidic acid (lpa), is an intermediate of de novo biosynthesis of glycerophospholipids and triacylglycerol. lpa is also attracting much attention because of its growth stimulating effects. here we report cloning of murine cdna encoding 1-agp acyltransferase (1-agpat), which converts lpa into phosphatidic acid by incorporating acyl moiety at an-2 position. the cdna contains an open reading frame coding for 285 amino acids, with highly ...19979299423
uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin.mitochondrial uncoupling proteins (ucps) are transporters that are important for thermogenesis. the net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from atp synthesis. we have cloned a third member of the ucp family, ucp3. ucp3 is expressed at high levels in muscle and rodent brown adipose tissue. overexpression in yeast reduced the mitochondrial membrane potential, showing that ucp3 is a functional uncoupling protein. ucp3 r ...19979305858
the mouse histone h1 genes: gene organization and differential regulation.there are six mouse histone h1 genes present in the histone gene cluster on mouse chromosome 13. these genes encode five histone h1 variants expressed in somatic cells, h1a to h1e, and the testis-specific h1t histone. two of the genes that have not been assigned previously to the five somatic h1 subtypes have been identified as encoding the h1b and h1d subtypes. three of the h1 genes, h1a, h1c and h1t, are present on an 80 kb segment of dna that contains nine core histone genes. two others, h1d ...19979300059
identification and characterization of two novel sh2 domain-containing proteins from a yeast two hybrid screen with the abl tyrosine kinase.to further our understanding of the molecular mechanism of bcr-abl mediated transformation, a yeast two hybrid screen was used to identify proteins binding to the abl tyrosine kinase. two partial cdnas encoding novel sh2 domain-containing proteins were cloned and designated shd and she. both have homology to shb, a previously reported sh2 domain-containing protein. northern blot analysis showed that she is expressed in heart, lung, brain, and skeletal muscle, while expression of shd is restricte ...19979315092
snf2beta-brg1 is essential for the viability of f9 murine embryonal carcinoma cells.the yeast and animal snf-swi and related multiprotein complexes are thought to play an important role in processes, such as transcription factor binding to regulatory elements, which require nucleosome remodeling in order to relieve the repressing effect of packaging dna in chromatin. there are two mammalian homologs of the yeast snf2-swi2 subunit protein, snf2alpha-brm and snf2beta-brg1, and overexpression of either one of them has been shown to enhance transcriptional activation by glucocortic ...19979315656
myostatin maps to the interval containing the bovine mh locus.myostatin (gdf-8) is a member of the transforming growth factor-beta superfamily and plays a role in muscle growth and development. mice having targeted disruption of this gene display marked increases in muscle mass, a phenotype similar to the muscular hypertrophy (mh) in several cattle breeds. physical mapping data developed from yac clones indicate the bovine myostatin gene lies close to the centromere of bovine chromosome (chr) 2 (bta2) at 2q11, indistinguishable from the cytogenetic locatio ...19979321467
failure to confirm estrogenic activity for benzoic acid and clofibrate: implications for lists of endocrine-disrupting agentsearlier reports that benzoic acid is uterotrophic to the rat and mouse and that clofibrate is uterotrophic to the rat have not been confirmed. the studies reported here involved the use of a range of test protocols and dose levels, including the protocols/dose levels used by the original investigators. in addition, both chemicals were inactive in a human estrogen receptor (heralpha) yeast estrogenicity assay. it is concluded that benzoic acid and clofibrate are not estrogenic in the assays used ...19979325211
polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin induce intrachromosomal recombination in vitro and in vivo.polychlorinated aromatic hydrocarbons such as polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd) are extremely stable and widely distributed environmental pollutants. these chemicals are animal carcinogens and probable human carcinogens, and tcdd is possibly one of the most potent toxins ever evaluated by the united states environmental protection agency. polychlorinated aromatic hydrocarbons score negatively in most genotoxicity assays, including the ames (salmonella) assa ...19979331101
isolation and characterization of pbp, a protein that interacts with peroxisome proliferator-activated receptor.in an attempt to identify cofactors that could possibly influence the transcriptional activity of peroxisome proliferator-activated receptors (ppars), we used a yeast two-hybrid system with gal4-ppargamma as bait to screen a mouse liver cdna library and have identified steroid receptor coactivator-1 (src-1) as a ppar transcriptional coactivator. we now report the isolation of a cdna encoding a 165-kda ppargamma-binding protein, designated pbp which also serves as a coactivator. pbp also binds to ...19979325263
the third member of the tetrahymena cct subunit gene family, tpcct alpha, encodes a component of the hetero-oligomeric chaperonin complex.the sequence of a third member of the tetrahymena pyriformis chaperonin cct ('chaperonin containing tcp1') subunit gene family is presented. this gene, designated tpcct alpha, is the orthologue of the mouse chaperonin gene tcp1/cct alpha. to characterize the cct complex in this ciliate, we have produced polyclonal antibodies against synthetic peptides based on c-terminal sequences deduced from the primary sequences of the tpcct alpha, tpcct gamma and tpcct eta subunits. we have also used polyclo ...19979337846
casp, a novel, highly conserved alternative-splicing product of the cdp/cut/cux gene, lacks cut-repeat and homeo dna-binding domains, and interacts with full-length cdp in vitro.human cdp/cut and its murine counterpart, cux1/cdp are homeodomain repressor proteins in the family of drosophila cut. northern blot analysis reveals complex alternative splicing, including forms too small to encode the full 1505 amino acid protein. we have characterized a cdp/cut alternatively spliced cdna (casp) of 3.4 kb. human casp, a predicted 678 amino acid polypeptide, shares 400 amino acids with cdp, but has an alternate n terminal exon of 20 aa, and the c-terminal 258 amino acids diverg ...19979332351
genomic organization and functional analysis of the murine protein phosphatase 1c gamma (ppp1cc) gene.protein phosphatase 1 holoenzymes are composed of catalytic subunits in combination with various regulatory subunits. in rodents, four different catalytic isoforms are known, pp1c alpha, -delta, -gamma 1, and -gamma 2. here we describe the genomic organization of the murine ppp1cc gene that encodes the pp1c gamma 1 and pp1c gamma 2 isoforms. we determined that ppp1cc maps to f1.2-g1.2 on chromosome 5 by fish mapping. southern hybridization and analysis of cross-hybridizing genomic clones reveale ...19979339378
failure to confirm estrogenic activity for benzoic acid and clofibrate: implications for lists of endocrine-disrupting agents.earlier reports that benzoic acid is uterotrophic to the rat and mouse and that clofibrate is uterotrophic to the rat have not been confirmed. the studies reported here involved the use of a range of test protocols and dose levels, including the protocols/dose levels used by the original investigators. in addition, both chemicals were inactive in a human estrogen receptor (her alpha) yeast estrogenicity assay. it is concluded that benzoic acid and clofibrate are not estrogenic in the assays used ...19979339486
severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in cc chemokine receptor 2.cc chemokine receptor 2 (ccr2) is a prominent receptor for the monocyte chemoattractant protein (mcp) group of cc chemokines. mice generated by gene targeting to lack ccr2 exhibit normal leukocyte rolling but have a pronounced defect in mcp-1-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. constitutive macrophage trafficking into the peritoneal cavity was not significantly different between ccr2-deficient and wild-type mice. however, after intrap ...19979342361
purification and characterization of the human sr 31747a-binding protein. a nuclear membrane protein related to yeast sterol isomerase.sr 31747a, defined as a sigma ligand, is a novel immunosuppressive agent that blocks proliferation of human and mouse lymphocytes. using a radiolabeled chemical probe, we here purified a target of sr 31747a and called it sr 31747a-binding protein (sr-bp). purified sr-bp retained its binding properties and migrated on sds-polyacrylamide gel as a mr 28,000 protein. cloning of the cdna encoding human sr-bp shows an open reading frame for a 223-amino acid protein, which is homologous to the recently ...19979341151
a gene spans the pseudoautosomal boundary in mice.the x and y chromosomes of the mouse, like those of other mammals, are heteromorphic over most of their length, but at the distal ends of the chromosomes is a region of sequence identity, the pseudoautosomal region (par), where the chromosomes pair and recombine during male meiosis. the point at which the par diverges into x- and y-specific sequences is called the pseudoautosomal boundary. we have completed a genomic walk from the x-specific amelogenin gene to the par. analysis of this region re ...19979342357
identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast vps1p and dnm1p.the dynamin family of gtp-binding proteins are implicated in vesicular transport. these include mammalian dynamins i, ii, iii, and yeast vps1p and dnm1p. dynamin is involved in the formation of clathrin-coated vesicles at the plasma membrane. on the other hand, vps1p and dnm1p appear to be involved in transport from the late golgi compartment to vacuoles and in an endocytic process, respectively. in this study, we identified a novel human protein, named dnm1p/vps1p-like protein (dvlp). it resemb ...19979348079
rapamycin and p53 act on different pathways to induce g1 arrest in mammalian cells.certain growth regulatory kinases contain a common domain related to the phospho-inositol 3 (pi-3) kinase catalytic site. these include the atm gene product, dna-pkcs, and the target of rapamycin (tor in yeast; and frap in mammalian cells). rapamycin inhibits growth factor signalling and induces g1 arrest in many cell types. some growth regulatory pi-3 kinases appear functionally linked to p53 and we have explored potential links between cellular effects induced by rapamycin and p53. in p53 null ...19979349496
identification of the fks1 gene of candida albicans as the essential target of 1,3-beta-d-glucan synthase inhibitors.pneumocandins and echinocandins are fungicidal antibiotics, currently in clinical development, that inhibit 1,3-beta-d-glucan synthase (gs) in several human fungal pathogens. we have identified a gene from the diploid organism candida albicans that encodes a target of these inhibitors. a 2.1-kb portion of this gene, designated cafks1, has significant homology to the saccharomyces cerevisiae fks1 and fks2 genes, which encode partially functionally redundant subunits of gs. to evaluate the role of ...19979371352
a novel gene involved in zinc transport is deficient in the lethal milk mouse.we have identified the gene responsible for the inherited zinc deficiency in the lethal milk (lm) mouse. the gene, here designated znt4, encodes a 430-amino-acid protein that is homologous to two proteins, znt2 and znt3, responsible for sequestration of zinc into endosomal/lysosomal compartments and synaptic vesicles, respectively. we show that the znt4 gene confers zinc resistance to a zinc-sensitive yeast strain and that it is abundantly expressed in the mammary epithelia and brain. the lethal ...19979354792
noc2, a putative zinc finger protein involved in exocytosis in endocrine cells.we have cloned a cdna encoding a novel protein of 302 amino acids (designated noc2, no c2 domain) that has 40.7% amino acid identity with and 77.9% similarity to the n-terminal region of rabphilin-3a, a target molecule of rab3a. however, unlike rabphilin-3a, noc2 lacks two c2 domains that are thought to interact with ca2+ and phospholipids. noc2 is expressed predominantly in endocrine tissues and hormone-secreting cell lines and at very low levels in brain. immunoblot analysis of subcellular fra ...19979367993
the phospholipid methyltransferases in yeast.in fungal microorganisms including fission yeast, schizosaccharomyces pombe and baker's yeast, saccharomyces cerevisiae, two enzymes are required to catalyze the synthesis of phosphatidylcholine (pc) from phosphatidylethanolamine (pe). the genes encoding the class i and class ii phospholipid n-methyltransferases (plmts) have been cloned from both yeasts. the class ii plmts catalyze the first methylation step from pe to phosphatidyl-monomethylethanolamine (pmme). representatives of the class ii t ...19979370325
the human beta globin locus introduced by yac transfer exhibits a specific and reproducible pattern of developmental regulation in transgenic mice.the human beta globin locus spans an 80-kb chromosomal region encompassing both the five expressed globin genes and the cis-acting elements that direct their stage-specific expression during ontogeny. sequences proximal to the genes and in the locus control region, 60 kb upstream of the adult beta globin gene, are required for developmental regulation. transgenic studies have shown that altering the structural organization of the locus disrupts the normal pattern of globin gene regulation. proce ...19979373272
interleukin-1beta secretion is impaired by inhibitors of the atp binding cassette transporter, abc1.the production of interleukin-1beta (il-1beta), a powerful mediator of inflammation, is tightly regulated at several levels. however, in some pathologic conditions, a pharmacologic treatment is required to control the toxicity of excessive extracellular il-1beta. because of the heavy side effects of most therapies used in il-1beta-mediated pathologies, a goal of pharmacologic research is the development of selective anti-il-1beta drugs. we show here that the sulfonylurea glyburide, currently use ...19979376570
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