Publications

mapping of pax-2 transcription activation domains.	pax genes encode transcription factors known to play crucial roles during the development of specific embryonic tissues. in humans and mice, several abnormalities have been linked to deficiencies in pax gene dosage, indicating that normal development is particularly sensitive to the level of pax gene expression. despite these facts, relatively little is known about how these proteins act as transcriptional regulators. in this study we define the transactivation domains of murine pax-2, an essent ...	1996	8702876
retinoid x receptor isotype identity directs human vitamin d receptor heterodimer transactivation from the 24-hydroxylase vitamin d response elements in yeast.	unlike estrogen and progesterone receptors that operate as homodimers on response elements, retinoid x receptors (rxrs) and vitamin d receptors (vdrs) can function as heterodimers. studies concerning the significance of heterodimeric partnerships are usually performed utilizing mammalian or insect cells. these cells express endogenous nuclear receptors, making it impossible to assign a role for one receptor subtype over another while studying the function of transfected receptor(s). yeast lacks ...	1996	8721985
biological insights through genomics: mouse to man.		1996	8567945
structural variation of the pseudoautosomal region between and within inbred mouse strains.	the pseudoautosomal region (par) is a segment of shared homology between the sex chromosomes. here we report additional probes for this region of the mouse genome. genetic and fluorescence in situ hybridization analyses indicate that one probe, par-4, hybridizes to the pseudoautosomal telomere and a minor locus at the telomere of chromosome 9 and that a pcr assay based on the par-4 sequence amplifies only the pseudoautosomal locus (dxyhgu1). the region detected by par-4 is structurally unstable; ...	1996	8552598
a mouse fas-associated protein with homology to the human mort1/fadd protein is essential for fas-induced apoptosis.	the fas cell surface receptor belongs to the tumor necrosis factor receptor family and can initiate apoptosis in a variety of cell types. using the fas cytoplasmic domain as bait in a yeast two-hybrid screening, we isolated a mouse cdna encoding a 205-amino-acid protein. its predicted protein sequence shows 68% identity and 80% similarity with the sequence of recently described human mort/fadd. this protein, most likely the mouse homolog of human fadd, associates with fas in vivo only upon the i ...	1996	8649383
identification, purification, and molecular cloning of autonomously replicating sequence-binding protein 1 from fission yeast schizosaccharomyces pombe.	autonomously replicating sequence (ars) elements of the fission yeast schizosaccharomyces pombe contain multiple imperfect copies of the consensus sequence reported by maundrell et al. [maundrell k., hutchison, a. & shall, s. (1988) embo j. 7, 2203-2209]. when cell free extracts of s. pombe were incubated with a dimer or tetramer of an oligonucleotide containing the ars consensus sequence, several complexes were detected using a gel mobility-shift assay. the proteins forming these complexes also ...	1996	8552670
cloning and characterization of the yeast hem14 gene coding for protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides.	protoporphyrinogen oxidase, which catalyzes the oxygen-dependent aromatization of protoporphyrinogen ix to protoporphyrin ix, is the molecular target of diphenyl ether type herbicides. the structural gene for the yeast protoporphyrinogen oxidase, hem14, was isolated by functional complementation of a hem14-1 protoporphyrinogen oxidase-deficient yeast mutant, using a novel one-step colored screening procedure to identify heme-synthesizing cells. the hem14-1 mutation was genetically linked to ura3 ...	1996	8621563
the orphan nuclear hormone receptor lxr alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling.	the yeast two-hybrid system was used to isolate novel cellular factors that interact with the mouse peroxisome proliferator-activated receptor alpha (pparalpha). one of the interacting clones isolated encoded lxralpha, a recently described human orphan nuclear hormone receptor. lxralpha bound directly to pparalpha, as well as to the common heterodimerization partner 9-cis-retinoic acid receptor (rxralpha). lxralpha did not form a dna binding complex with pparalpha on synthetic hormone response e ...	1996	8621574
a reca-like gene in drosophila melanogaster that is expressed at high levels in female but not male meiotic tissues.	the reca protein is the central enzyme in prokaryotic recombination. it catalyzes pairing and strand exchange between homologous dna molecules, and functions in both dna repair and genetic recombination. the reca-like proteins rad51 and dmc1 of yeast are both required for meiotic recombination and the former is also necessary for repair of double-strand breaks in vegetative cells. genes encoding rad51 homologs have been isolated recently from several higher eukaryotes. this paper describes the i ...	1996	8625736
the nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed srp1-nuclear localization sequence receptor proteins.	proteins are directed to the nucleus by their nuclear localization sequences (nlss) in a multistep process. the first step, which is to dock the nls-containing protein to the nuclear pore, is carried out in part by a recently identified nls receptor named srp1/importin-alpha. using the high mobility group (hmg) dna binding domain of human lymphoid enhancer factor-1 (hlef-1) as bait in a yeast two-hybrid screen, we have identified two different mouse srp1 proteins (pendulin/importin-alpha and msr ...	1996	8631802
the tc21 oncoprotein interacts with the ral guanosine nucleotide dissociation factor.	tc21 is a highly oncogenic member of the ras superfamily of small gtp binding proteins. we have used the yeast two hybrid system to identify proteins that interact with an oncogenic form of the tc21 protein. cdna clones encoding the carboxy-terminal region of the ralgds protein were isolated from human b-cell and hela cdna libraries. ralgds is an exchange factor that stimulates gdp dissociation from ral, another member of the ras superfamily of proteins. the interaction between ralgds to tc21 is ...	1996	8637701
a long-range regulatory element of hoxc8 identified by using the pclasper vector.	hox genes are located in highly conserved clusters. the significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other hox genes. this hypothesis is supported by studies on several hox genes in which even large genomic regions immediately surrounding the gene fail to direct the complete expression pattern in transgenic mice. in particular, previous studies have identified proximal regula ...	1996	8637890
[progress of research on tumor suppressor genes].	the multistage model of carcinogenesis during tumor progression requires that there should be consecutive genetic abnormalities of both oncogenes and tumor suppressor genes. as is true of the protein products of oncogenes, tumor suppressor proteins are found to have various cellular functions. they are involved in the regulation of adhesion, cell-cell interaction, and cytoplasmic signal transducers as well as nuclear transcription factors. the recently identified hmsh2 (human muts homolog 2) gen ...	1996	8641669
effect of growth condition on in-vitro susceptibility of shigella dysenteriae type 1 killing by murine peritoneal macrophages.	the intracellular fate of shigella dysenteriae type 1 strains grown in casamino acid-yeast extract (cye) broth and nutrient broth (nb) was studied in casein-elicited mouse peritoneal macrophages. virulent strains 14731 and w30864 cultured in nb and opsonised with normal mouse serum were susceptible to killing by peritoneal macrophages (66 sem 1.7% killing by 2 h). in contrast, both strains grown in cye broth and opsonised with normal mouse serum showed resistance to killing by peritoneal macroph ...	1996	8642582
mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma.	the t(2;13) translocation of alveolar rhabdomyosarcoma results in tumor-specific expression of a chimeric transcription factor containing the n-terminal dna-binding domain of pax3 and the c-terminal transactivation domain of fkhr. here we have tested the hypothesis that pax3-fkhr gains function relative to pax3 as a consequence of switching pax3 and fkhr transactivation domains, which were previously shown to have similar potency but distinct structural motifs. in transient cotransfection assays ...	1996	8643596
trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.	several human neurological disorders are associated with proteins containing abnormally long runs of glutamine residues. strikingly, most of these proteins contain two or more additional long runs of amino acids other than glutamine. we screened the current human, mouse, drosophila, yeast, and escherichia coli protein sequence data bases and identified all proteins containing multiple long homopeptides. this search found multiple long homopeptides in about 12% of drosophila proteins but in only ...	1996	8643671
is gamma-actin a regulator of amino acid transport?	a mutated yeast cell line incapable of growth in minimal medium with proline as the sole nitrogen source was restored to normal growth by transfection with a cdna from mouse ehrlich cells. the cloned cdna (e51) was found to be 90% homologous to gamma-actin. immediately after transfection with e51 cdna, both alpha-aminoisobutyric acid (aib) and proline uptake in the mutated yeast were increased, particularly at ph 5. the expression of the same e51 cdna also enhanced amino acid uptake in xenopus l ...	1996	8764147
the hormone responsive region of mouse mammary tumor virus positions a nucleosome and precludes access of nuclear factor i to the promoter.	the mouse mammary tumor virus (mmtv) promoter is transcriptionally silent prior to hormonal induction, partly because its organization into phased nucleosomes precludes access of transcription factors to their cognate sites. a t47d-derived cell line carrying a single integrated copy of the mmtv promoter exhibited a positioned nucleosome, which prevented binding of nuclear factor i (nfi). to study the molecular mechanisms controlling promoter accessibility we have made use of a strong chimeric tr ...	1996	8645614
characterization of the functional gene encoding mouse class iii alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) and an unexpressed processed pseudogene with an intact open reading frame.	multiple forms of vertebrate alcohol dehydrogenase (adh) have been identified, but only one form, class iii adh, has been conserved in all organisms studied. class iii adh functions in vitro as a glutathione-dependent formaldehyde dehydrogenase, which suggests that this was the original function that drove the evolution of adh. genetic analysis of class iii adh in yeast supports this view, but such studies are lacking in higher eukaryotes. the mouse adh family has been previously analyzed and it ...	1996	8647091
complementation of the beige mutation in cultured cells by episomally replicating murine yeast artificial chromosomes.	chédiak-higashi syndrome in man and the beige mutation of mice are phenotypically similar disorders that have profound effects upon lysosome and melanosome morphology and function. we isolated two murine yeast artificial chromosomes (yacs) that, when introduced into beige mouse fibroblasts, complement the beige mutation. the complementing yacs exist as extrachromosomal elements that are amplified in high concentrations of g418. when yac-complemented beige cells were fused to human chédiak-higash ...	1996	8650191
rhotekin, a new putative target for rho bearing homology to a serine/threonine kinase, pkn, and rhophilin in the rho-binding domain.	using a mouse embryo cdna library, we conducted a two-hybrid screening to identify new partners for the small gtpase rho. one clone obtained by this procedure contained a novel cdna of 291 base pairs and interacted strongly with rhoa and rhoc, weakly with rhob, and not at all with rac1 and cdc42hs. full-length cdnas were then isolated from a mouse brain library. while multiple splicing variants were common, we identified three cdnas with an identical open reading frame encoding a 61-kda protein ...	1996	8662891
mouse p170 is a novel phosphatidylinositol 3-kinase containing a c2 domain.	phosphatidylinositol (pi) 3-kinases catalyze the formation of 3'-phosphoinositides, which appear to promote cellular responses to growth factors and such membrane trafficking events as insulin-stimulated translocation of intracellular glucose transporters. we report here the cloning of a novel pi 3-kinase, p170, from cdna of insulin-sensitive mouse 3t3-l1 adipocytes. mouse p170 utilizes pi and to a limited extent pi 4-p as substrates, in contrast to the pi-specific yeast vps34 homolog ptdins 3-k ...	1996	8663140
antisense inhibition of the rad51 enhances radiosensitivity.	the mammalian rad51 gene is a homologue of the yeast rad51 and e. coli reca genes, which are involved in recombination and dna repair. we examined the role of rad51 protein in mouse cells using rad51 antisense phosphorothioate oligonucleotides (odns). the extraluminal delivery of 50 nm or 100 nm of antisense odns with lipofection to mouse cells resulted 90% suppression of rad51 protein expression. the antisense odns significantly inhibited the cell growth and the treated cells became more sensit ...	1996	8670299
cloning, structure and mrna expression of human cctg, which encodes the chaperonin subunit cct gamma.	we describe the cloning, dna sequence analysis and mrna expression analysis of human cctg (hscctg), a gene that encodes the gamma-subunit of the eukaryotic cytosolic 'chaperonin-containing tcp-1' (cct). partial clones representing the 3' region of hscctg cdna were isolated from a human kidney cdna library, and the missing 5' region was amplified directly from human kidney cdna. the cctg mrna transcript is expressed in numerous human and mouse tissues and, like tcp-1/ccta, cctg mrna is expressed ...	1996	8573069
identification of a novel family of ubiquitin-conjugating enzymes with distinct amino-terminal extensions.	the ubiquitin/proteasome system is the main eukaryotic nonlysosomal protein degradation system. substrate selectivity of this pathway is thought to be mediated in part by members of a large family of ubiquitin-conjugating (e2) enzymes, which catalyze the covalent attachment of ubiquitin to proteolytic substrates. e2 enzymes have a conserved approximately 150-residue so-called ubc domain, which harbors the cysteine residue required for enzyme-ubiquitin thioester formation. some e2 enzymes possess ...	1996	8576256
high-avidity human igg kappa monoclonal antibodies from a novel strain of minilocus transgenic mice.	human immunoglobulin transgenic mice provide a method of obtaining human monoclonal antibodies (mabs) using conventional hybridoma technology. we describe a novel strain of human immunoglobulin transgenic mice and the use of this strain to generate multiple high-avidity human sequence igg kappa mabs directed against a human antigen. the light chain transgene is derived in part from a yeast artificial chromosome clone that includes nearly half of the germline human v kappa region. in addition, th ...	1996	9631008
mammalian rad51 protein: a reca homologue with pleiotropic functions.	during the last years, homologues of e coli reca have been cloned in numerous species including man. these rad51 proteins share sequence as well as functional homologies with the bacterial protein. human rad51 (hsrad51) is able to catalyze strand exchange in vitro between homologous dnas, but with a lower efficiency compared to that of reca. this suggests the requirement of additional factors. a very interesting feature of rad51 is its essential role in mouse which could mean that it has gained ...	1997	9466696
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 ...	1997	9034326
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 ...	1997	9075711
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 ...	1997	9047351
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 ...	1997	9079683
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 ...	1997	9139716
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 ...	1997	9099876
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 ...	1997	9130713
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 ...	1997	9102632
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. ...	1997	9076656
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 ...	1997	9050988
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 ...	1997	9115172
dbl family proteins.		1997	9061011
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 ...	1997	9121478
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 ...	1997	9150136
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 ...	1997	9122188
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 ...	1997	9147654
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% ...	1997	9161407
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 ...	1997	9173976
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 ...	1997	9178502
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.	1997	9179435
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 ...	1997	9182581
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 ...	1997	9197411
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 ...	1997	9203580
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 ...	1997	9210379
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 ...	1997	9211850
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 ...	1997	9276729
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 ...	1997	9321467
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 ...	1997	9182575
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 ...	1997	9212977
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 ...	1997	9214622
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 ...	1997	9224733
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 ...	1997	9227330
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 ...	1997	9228028
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 ...	1997	9252477
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 ...	1997	9256449
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 ...	1997	9256472
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 ...	1997	9271096
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 ...	1997	9272871
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 ...	1997	9288106
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 ...	1997	9233803
genetic and physical mapping of the mouse host resistance locus lgn1.		1997	9271671
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 ...	1997	9354792
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 ...	1997	9288972
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 (heralpha) yeast estrogenicity assay. it is concluded that benzoic acid and clofibrate are not estrogenic in the assays used ...	1997	9325211
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 ...	1997	9294720
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 ...	1997	9298905
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 ...	1997	9325263
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 ...	1997	9299423
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 ...	1997	9300059
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 ...	1997	9305858
in vivo analyses of rna polymerase i termination in schizosaccharomyces pombe.	recent studies on the termination of rdna transcription by rna polymerase i in saccharomyces cerevisiae and schizosaccharomyces pombe have suggested a more complex mechanism then previously described in higher eukaryotes. termination appears to occur when a dna-bound reb1 protein molecule induces polymerase to pause in the context of a release element [see reeder,r.h. and lang,w. (1994) mol. microbiol ., 12, 11-15]. because these conclusions in yeast were based entirely on in vitro analyses, we ...	1997	9396822
the proofreading domain of escherichia coli dna polymerase i and other dna and/or rna exonuclease domains.	prior sequence analysis studies have suggested that bacterial ribonuclease (rnase) ds comprise a complete domain that is found also in homo sapiens polymyositis-scleroderma overlap syndrome 100 kda autoantigen and werner syndrome protein. this rnase d 3'-->5' exoribonuclease domain was predicted to have a structure and mechanism of action similar to the 3'-->5' exodeoxyibonuclease (proofreading) domain of dna polymerases. here, hidden markov model (hmm) and phylogenetic studies have been used to ...	1997	9396823
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 ...	1997	9315092
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 ...	1997	9315656
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 ...	1997	9331101
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 ...	1997	9332351
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 ...	1997	9223278
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 ...	1997	9337846
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 ...	1997	9339378
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 ...	1997	9339486
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 ...	1997	9341151
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 ...	1997	9342357
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 ...	1997	9348079
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 ...	1997	9122214
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 ...	1997	9367993
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 ...	1997	9342361
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 ...	1997	9370325
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 ...	1997	9349496
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 ...	1997	9371352
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 ...	1997	9373272
no evidence for involvement of mouse protein-tyrosine phosphatase-bas-like fas-associated phosphatase-1 in fas-mediated apoptosis.	recently, one of the pdz domains in the cytosolic protein-tyrosine phosphatase fas-associated phosphatase-1 (fap-1)/protein-tyrosine phosphatase-bas (ptp-bas) was shown to interact with the carboxyl-terminal ts-l-v peptide of the human fas receptor (sato, t., irie, s., kitada, s., and reed, j. c. (1995) science 268, 411-415), suggesting a role for protein (de)phosphorylation in fas signaling. to investigate whether this interaction is conserved in mouse, we performed yeast two-hybrid interaction ...	1997	9374505
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 ...	1997	9376570
atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes.	checkpoint pathways prevent cell-cycle progression in the event of dna lesions. checkpoints are well defined in mitosis, where lesions can be the result of extrinsic damage, and they are critical in meiosis, where dna breaks are a programmed step in meiotic recombination. in mitotic yeast cells, the chk1 protein couples dna repair to the cell-cycle machinery. the atm and atr proteins are mitotic cell-cycle proteins that also associate with chromatin during meiotic prophase i. the genetic and reg ...	1997	9382850