Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| progressive loss of sirt1 with cell cycle withdrawal. | sir2 is an nad+-dependent deacetylase that regulates lifespan in yeast, worms and flies. the mammalian orthologs of sir2 include sirt1 in humans and mice. in this study, we analyzed the level of sirt1 in human lung fibroblasts (imr90) and mouse embryonic fibroblasts (mefs) from mice with normal, accelerated, and delayed aging. sirt1 protein, but not mrna, decreased significantly with serial cell passage in both human and murine cells. mouse sirt1 decreased rapidly in prematurely senescent (p44 t ... | 2006 | 16939484 |
| [methods for monitoring macroautophagy]. | 2006 | 16922435 | |
| a novel krüppel related factor consisting of only a krab domain is expressed in the murine trigeminal ganglion. | the largest family of zinc-finger (znf) transcription factors is that containing the krüppel-associated box, or krab domain. the amino-terminal krab domain of these proteins functions as a transcriptional repressor with the downstream znf motifs providing dna-binding specificity. here we report the identification and characterization of a novel murine krüppel-related factor (klf), mif1, which contains a krab domain but lacks a znf motif. western blot analysis identified mif1-like proteins in the ... | 2006 | 16904636 |
| genome comparison using gene ontology (go) with statistical testing. | automated comparison of complete sets of genes encoded in two genomes can provide insight on the genetic basis of differences in biological traits between species. gene ontology (go) is used as a common vocabulary to annotate genes for comparison. current approaches calculate the fold of unweighted or weighted differences between two species at the high-level go functional categories. however, to ensure the reliability of the differences detected, it is important to evaluate their statistical si ... | 2006 | 16901353 |
| molecular dissection of the munc18c/syntaxin4 interaction: implications for regulation of membrane trafficking. | sec1p/munc18 (sm) proteins are believed to play an integral role in vesicle transport through their interaction with snares. different sm proteins have been shown to interact with snares via different mechanisms, leading to the conclusion that their function has diverged. to further explore this notion, in this study, we have examined the molecular interactions between munc18c and its cognate snares as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma m ... | 2006 | 16899085 |
| interactions between e2f1 and sirt1 regulate apoptotic response to dna damage. | the nicotinamide adenine dinucleotide (nad)-dependent deacetylase sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. the mammalian homologue of sir2 (sirt1) regulates p53, nf-kappab and forkhead transcription factors, and is implicated in stress response. this report shows that the cell-cycle and apoptosis regulator e2f1 induces sirt1 expression at the transcriptional level. furthermore, sirt1 binds to e2f1 and inhi ... | 2006 | 16892051 |
| genetic structure and evolution of the vps25 family, a yeast escrt-ii component. | vps25p is the product of yeast gene vps25 and is found in an endosomal sorting complex required for transport (escrt)-ii, along with vps22p and vps36p. this complex is essential for sorting of ubiquitinated biosynthetic and endosomal cargoes into endosomes. | 2006 | 16889659 |
| using annotated peptide mass spectrum libraries for protein identification. | a system for creating a library of tandem mass spectra annotated with corresponding peptide sequences was described. this system was based on the annotated spectra currently available in the global proteome machine database (gpmdb). the library spectra were created by averaging together spectra that were annotated with the same peptide sequence, sequence modifications, and parent ion charge. the library was constructed so that experimental peptide tandem mass spectra could be compared with those ... | 2006 | 16889405 |
| the evolutionarily conserved domain of beclin 1 is required for vps34 binding, autophagy and tumor suppressor function. | atg6/beclin 1 is an evolutionarily conserved protein family that has been shown to function in vacuolar protein sorting (vps) in yeast; in autophagy in yeast, drosophila, dictyostelium, c.elegans, and mammals; and in tumor suppression in mice. atg6/beclin 1 is thought to function as a vps and autophagy protein as part of a complex with class iii phosphatidylinositol 3'-kinase (pi3k)/vps34. however, nothing is known about which domains of atg6/beclin 1 are required for its functional activity and ... | 2005 | 16874027 |
| bacello: a balanced subcellular localization predictor. | the knowledge of the subcellular localization of a protein is fundamental for elucidating its function. it is difficult to determine the subcellular location for eukaryotic cells with experimental high-throughput procedures. computational procedures are then needed for annotating the subcellular location of proteins in large scale genomic projects. | 2006 | 16873501 |
| inactive full-length p53 mutants lacking dominant wild-type p53 inhibition highlight loss of heterozygosity as an important aspect of p53 status in human cancers. | over 1000 different mutants of the tumor suppressor protein p53 with one amino acid change in the core domain have been reported in human cancers. in mouse knock-in models, two frequent mutants displayed loss of wild-type (wt) p53 function, inhibition of wt p53 and wt p53-independent gain of function. the remaining mutants have been systematically characterized for loss of wt p53 function, but not other phenotypes. we report the concomitant assessment of loss of function and interference with wt ... | 2007 | 16861262 |
| rev1 protein interacts with pcna: significance of the rev1 brct domain in vitro and in vivo. | rev1 protein, a eukaryotic member of the y family of dna polymerases, is involved in the tolerance of dna damage by translesion dna synthesis. it is unclear how rev1 is recruited to replication foci in cells. here, we report that mouse rev1 can bind directly to pcna and that monoubiquitylation of pcna enhances this interaction. the interaction between rev1 protein and pcna requires a functional brct domain located near the n terminus of the former protein. deletion or mutational inactivation of ... | 2006 | 16857592 |
| snx5, as a mind bomb-binding protein, is expressed in hematopoietic and endothelial precursor cells in zebrafish. | notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. previously, we identified a novel component of the notch signaling pathway in zebrafish, mind bomb, which encodes an e3 ubiquitin ligase essential for notch signal activation. further studies showed that mind bomb(-/-) mouse embryos exhibited pan-notch phenotypes in various tissues, suggesting that mind bomb function is conserved in mammals. therefore we sought to understand the variou ... | 2006 | 16857196 |
| yogy: a web-based, integrated database to retrieve protein orthologs and associated gene ontology terms. | we present yogy a web-based resource for orthologous proteins from nine eukaryotic organisms: homo sapiens, mus musculus, rattus norvegicus, arabidopsis thaliana, drosophila melanogaster, caenorhabditis elegans, plasmodium falciparum, schizosaccharomyces pombe and saccharomyces cerevisiae. using a gene name from any of these organisms as a query, this database provides comprehensive, combined information on orthologs in other species using data from five independent resources: kogs, inparanoid, ... | 2006 | 16845020 |
| ptarget: a web server for predicting protein subcellular localization. | the ptarget web server enables prediction of nine distinct protein subcellular localizations in eukaryotic non-plant species. predictions are made using a new algorithm [c. guda and s. subramaniam (2005) ptarget [corrected] a new method for predicting protein subcellular localization in eukaryotes. bioinformatics, 21, 3963-3969], which is primarily based on the occurrence patterns of location-specific protein functional domains in different subcellular locations. we have implemented a relational ... | 2006 | 16844995 |
| mitochondrial rhomboid parl regulates cytochrome c release during apoptosis via opa1-dependent cristae remodeling. | rhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. presenilin-associated rhomboid-like (parl) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. parl-/- mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic atrophy leading to cachectic death. atrophy is sustained by increased apoptosis, both in and ex vivo. pa ... | 2006 | 16839884 |
| resolution of chiasmata in oocytes requires separase-mediated proteolysis. | in yeast, resolution of chiasmata in meiosis i requires proteolytic cleavage along chromosome arms of cohesin's rec8 subunit by separase. since activation of separase by the anaphase-promoting complex (apc/c) is supposedly not required for meiosis i in xenopus oocytes, it has been suggested that animal cells might resolve chiasmata by a separase-independent mechanism related to the so-called "prophase pathway" that removes cohesin from chromosome arms during mitosis. by expressing cre recombinas ... | 2006 | 16839882 |
| mammalian tak1 activates snf1 protein kinase in yeast and phosphorylates amp-activated protein kinase in vitro. | the snf1/amp-activated protein kinase (ampk) family is important for metabolic regulation and is highly conserved from yeast to mammals. the upstream kinases are also functionally conserved, and the ampk kinases lkb1 and ca2+/calmodulin-dependent protein kinase kinase activate snf1 in mutant yeast cells lacking the native snf1-activating kinases, sak1, tos3, and elm1. here, we exploited the yeast genetic system to identify members of the mammalian ampk kinase family by their function as snf1-act ... | 2006 | 16835226 |
| inhibition of atf4 transcriptional activity by fiat/gamma-taxilin modulates bone mass accrual. | the basic domain-leucine zipper protein, activating transcription factor 4 (atf4), was recently shown to control key aspects of osteoblast biology. atf4 regulates the timely onset of osteoblast differentiation, the synthesis of type i collagen, and the transcription of the osteocalcin and rankl (receptor activator of nfkappa-b ligand) genes. accordingly, the levels and activity of atf4 are under tight control through mechanisms that include protein stability and phosphorylation. we have uncovere ... | 2006 | 16831913 |
| whirlin complexes with p55 at the stereocilia tip during hair cell development. | hearing in mammals depends upon the proper development of actin-filled stereocilia at the hair cell surface in the inner ear. whirlin, a pdz domain-containing protein, is expressed at stereocilia tips and, by virtue of mutations in the whirlin gene, is known to play a key role in stereocilia development. we show that whirlin interacts with the membrane-associated guanylate kinase (maguk) protein, erythrocyte protein p55 (p55). p55 is expressed in outer hair cells in long stereocilia that make up ... | 2006 | 16829577 |
| inositol phosphate metabolomics: merging genetic perturbation with modernized radiolabeling methods. | recent discoveries that provide a link between inositol phosphate (ip) signaling and fundamental cellular processes evoke many exciting new hypotheses about ip function, and underscore the importance of understanding how ip synthesis is regulated. central to studies of ip metabolism is the essential development of efficient, fast, and reproducible methods for quantitative analysis of ips in systems ranging from simple cell cultures to more complex tissues and whole organisms. additionally, in ma ... | 2006 | 16829132 |
| control of transcription factor activity and osteoblast differentiation in mammalian cells using an evolved small-molecule-dependent intein. | inteins are naturally occurring protein elements that catalyze their own excision from within a larger protein together with the ligation of the flanking "extein" sequences. previously we reported the directed evolution of an intein-based molecular switch in which intein splicing in yeast cells was made dependent on the cell-permeable small molecule 4-hydroxytamoxifen (4-ht). here we show that these evolved inteins are effective means of rendering protein function and biological signaling pathwa ... | 2006 | 16819890 |
| saccharomyces boulardii inhibits erk1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against clostridium difficile toxin a-induced enteritis. | saccharomyces boulardii (sb), a probiotic yeast, protects against intestinal injury and inflammation caused by a wide variety of enteric pathogens, including clostridium difficile. given the broad range of protective effects of sb in multiple gastrointestinal disorders, we hypothesize that sb modulates host signaling pathways involved in intestinal inflammatory responses. in this study, we found that sb culture supernatant (sbs) inhibits interleukin-8 production induced by c. difficile toxin a o ... | 2006 | 16816386 |
| protein phosphatase 6 subunit with conserved sit4-associated protein domain targets ikappabepsilon. | protein ser/thr phosphatases compose a ppp family that includes type-2 pp2a, pp4, and pp6, each with essential functions. the human pp6 gene rescues sit4(ts) mutants of saccharomyces cerevisiae, and sit4 phosphatase function depends on multiple sit4-associated protein (sap) subunits. we report here finding a saps sequence domain encoded in only a single gene each in schizosaccharomyces pombe, caenorhabditis elegans, and drosophila but in three distinct open reading frames in xenopus, mus musculu ... | 2006 | 16769727 |
| resveratrol--a boon for treating alzheimer's disease? | resveratrol, a red wine polyphenol, is known to protect against cardiovascular diseases and cancers, as well as to promote antiaging effects in numerous organisms. it also modulates pathomechanisms of debilitating neurological disorders, such as strokes, ischemia, and huntington's disease. the role of resveratrol in alzheimer's disease is still unclear, although some recent studies on red wine bioactive compounds suggest that resveratrol modulates multiple mechanisms of alzheimer's disease patho ... | 2006 | 16766037 |
| yke4 (yil023c) encodes a bidirectional zinc transporter in the endoplasmic reticulum of saccharomyces cerevisiae. | yil023c encodes a member of the slc39a, or zip, family, which we refer to as yeast ke4 (yke4) after its mouse ortholog. yke4p was localized to the endoplasmic reticulum (er) membrane using yke4p-specific antiserum. yke4 is not an essential gene; however, deletion of yke4 resulted in a sensitivity to calcofluor white and poor growth at 36 degrees c on respiratory substrates containing high zinc. overexpression of transition metal transporters zrc1p and cot1p or the mouse orthologue mke4 in deltay ... | 2006 | 16760462 |
| integrin cytoplasmic domain-associated protein-1 (icap-1) interacts with the rock-i kinase at the plasma membrane. | the integrin cytoplasmic domain-associated protein-1 (icap-1) binds via its c-terminal ptb (phosphotyrosine-binding) domain to the cytoplasmic tails of beta1 but not other integrins. using the yeast two-hybrid assay, we found that icap-1 binds the rock-i kinase, an effector of the rhoa gtpase. by coimmunoprecipitation we show that icap-1 and rock form complexes in cells and that icap-1 contains two binding sites for rock. in cells transfected with both icap-1 and rock, the proteins colocalized a ... | 2006 | 16741948 |
| differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver x receptor-beta, and retinoid x receptor-alpha. | administration of ammonium salts of perfluorooctanoate (pfoa) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (nr) peroxisome proliferator-activated receptor-alpha (pparalpha). due to its fatty acid structure, pfoa may activate other nrs, such as pparbeta, ppargamma, liver x receptor (lxr), or retinoid x receptor (rxr). in this study, the activation of human, mouse, and rat pparalpha, pparbeta, ppargamma, lxrbeta, and ... | 2006 | 16731579 |
| differential localization of complement component 3 within the capsular matrix of cryptococcus neoformans. | the polysaccharide capsule of cryptococcus neoformans is a powerful activator of the complement system. the goal of the present study was to assess serum and cellular variables that influence the sites for c3 binding within the capsular matrix. confocal microscopy using fluorophore-labeled polyclonal anti-c3 and anticapsular monoclonal antibodies and rosetting of fluorescent microspheres coated with anti-c3 were used to identify sites of c3 binding relative to the capsular edge. the results show ... | 2006 | 16714537 |
| the coiled-coil protein shrub controls neuronal morphogenesis in drosophila. | the diversity of neuronal cells, especially in the size and shape of their dendritic and axonal arborizations, is a striking feature of the mature nervous system. dendritic branching is a complex process, and the underlying signaling mechanisms remain to be further defined at the mechanistic level. here we report the identification of shrub mutations that increased dendritic branching. single-cell clones of shrub mutant dendritic arborization (da) sensory neurons in drosophila larvae showed ecto ... | 2006 | 16713958 |
| nuclear pore complex assembly and maintenance in pom121- and gp210-deficient cells. | so far, pom121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (npcs) within the lipid bilayer of the nuclear envelope (ne) and, thus, are excellent candidates for initiating the npc assembly process. indeed, we demonstrate that pom121 can recruit several nucleoporins, such as nup62 or nup358, to ectopic assembly sites. it thus appears to act as a nucleation site for the assembly of npc substructures. nonetheless, we observed functional npcs and intact nes in se ... | 2006 | 16702234 |
| a mouse trapp-related protein is involved in pigmentation. | we identified a new spontaneous recessive mutation in the mouse, mhyp (mosaic hypopigmentation), in a screen for novel proviral integration sites in a multiple ecotropic provirus mapping stock. integration of an 8.4-kb retrovirus results in mosaic loss of coat pigment in mhyp homozygotes. patchy loss of pigmentation in the retinal pigmented epithelial layer of the eye with abnormal melanosomes is also evident. we mapped mhyp to mouse chromosome 7 and cloned the underlying gene. mhyp is a defect ... | 2006 | 16697553 |
| the nuclear hormone receptor farnesoid x receptor (fxr) is activated by androsterone. | farnesoid x receptor (fxr) uses bile acids as endogenous ligands. here, we demonstrate that androsterone, a metabolic product of testosterone, is also an fxr ligand. treatment of castrated male mice with androsterone induced expression of the fxr target gene small heterodimer partner (shp). in mouse aml-12 hepatocytes, chenodeoxycholic acid (cdca) or androsterone induced shp expression with a similar kinetic pattern. the fxr antagonist guggulsterone blocked the induction of shp by androsterone i ... | 2006 | 16675527 |
| sun1 interacts with nuclear lamin a and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. | nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (ne) proteins that share a conserved c-terminal sun (sad1/unc-84 homology) domain. analysis of caenorhabditis elegans mutants has implicated unc-84 in actin-mediated nuclear positioning by regulating ne anchoring of a giant actin-bindi ... | 2006 | 16648470 |
| the swi/snf chromatin remodeling complex is essential for hyphal development in candida albicans. | the ability of dimorphic transition between yeast and hyphal forms in candida albicans is one of the vital determinants for its pathogenicity and virulence. we isolated c. albicans swi1 as a suppressor of the invasive growth defect in a saccharomyces cerevisiae mutant. expression of c. albicans swi1 in s. cerevisiae partially complemented the growth defect of a swi1 mutant in the utilization of glycerol. swi1 is in a complex with snf2 in c. albicans, and both proteins are localized in the nucleu ... | 2006 | 16647065 |
| suppressed disassembly of autolyzing p94/capn3 by n2a connectin/titin in a genetic reporter system. | p94/calpain 3 is a skeletal muscle-specific member of the ca(2+)-regulated cytosolic cysteine protease family, the calpains. defective p94 protease activity originating from gene mutations causes a muscular dystrophy called calpainopathy, indicating the indispensability of p94 for muscle survival. because of the existence of the p94-specific regions is1 and is2, p94 undergoes very rapid and exhaustive autolysis. to elucidate the physiological relevance of this unique activity, the autolytic prof ... | 2006 | 16627476 |
| evidence from knockout mice against physiologically significant aquaporin 8-facilitated ammonia transport. | aquaporin (aqp)8-facilitated transport of nh(3) has been suggested recently by increased nh(3) permeability in xenopus oocytes and yeast expressing human or rat aqp8. we tested the proposed roles of aqp8-facilitated nh(3) transport in mammalian physiology by comparative phenotype studies in wild-type vs. aqp8-null mice. aqp8-facilitated nh(3) transport was confirmed in mammalian cell cultures expressing rat or mouse aqp8, in which the fluorescence of a ph-sensing yellow fluorescent protein was m ... | 2006 | 16624991 |
| a recombination silencer that specifies heterochromatin positioning and ikaros association in the immunoglobulin kappa locus. | allelic exclusion ensures that individual b lymphocytes produce only one kind of antibody molecule. previous studies have shown that allelic exclusion of the mouse igkappa locus occurs by the combination of monoallelic silencing and a low level of monoallelic activation for rearrangement combined with a negative feedback loop blocking additional functional rearrangements. using yeast artificial chromosome-based single-copy isotransgenic mice, we have identified a cis-acting element that negative ... | 2006 | 16618599 |
| identification of the key lmo2-binding determinants on ldb1. | the overexpression of lim-only protein 2 (lmo2) in t-cells, as a result of chromosomal translocations, retroviral insertion during gene therapy, or in transgenic mice models, leads to the onset of t-cell leukemias. lmo2 comprises two protein-binding lim domains that allow lmo2 to interact with multiple protein partners, including lim domain-binding protein 1 (ldb1, also known as clim2 and nli), an essential cofactor for lmo proteins. sequestration of ldb1 by lmo2 in t-cells may prevent it bindin ... | 2006 | 16616188 |
| membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with c kinase 1 in a cerebellar purkinje neuron. | the glutamate receptor delta2 subunit (glurdelta2) is selectively expressed in cerebellar purkinje neurons (pns) and is involved in the long-term depression (ltd). however, little is known about the mechanism of its action. acute expression of the wild-type glurdelta2 in the glurdelta2-deficient pn rescued the induction of ltd, suggesting the direct role of glurdelta2 in ltd. to identify the critical region of glurdelta2 necessary for ltd, we constructed and expressed various mutant glurdelta2 p ... | 2006 | 16597715 |
| selective regulation of il-10 signaling and function by zymosan. | balanced activity of pro- and anti-inflammatory cytokines during innate immune responses is required to allow effective host defense while avoiding tissue damage and autoimmunity. induction of cytokine production after recognition of pathogen-associated molecular patterns (pamps) by innate immune cells has been well demonstrated, but modulation of cytokine function by pamps is not well understood. in this study we show that stimulation of macrophages with zymosan, which contains pamps derived fr ... | 2006 | 16585572 |
| the high-mobility-group domain of sox proteins interacts with dna-binding domains of many transcription factors. | sox proteins are widely believed to team up with other transcription factors as partner proteins to perform their many essential functions during development. in this study, yeast two-hybrid screens identified transcription factors as a major group of interacting proteins for sox8 and sox10. interacting transcription factors were very similar for these two group e sox proteins and included proteins with different types of dna-binding domains, such as homeodomain proteins, zinc finger proteins, b ... | 2006 | 16582099 |
| oog1, an oocyte-specific protein, interacts with ras and ras-signaling proteins during early embryogenesis. | we previously identified an oocyte-specific gene, oogenesin 1 (oog1), that encodes 326 amino acids containing a leucine zipper structure and a leucine-rich repeat. in the present study, to identify the interacting proteins of oog1, we performed a yeast two-hybrid screening using a gv-oocyte cdna library and found that ral guanine nucleotide dissociation stimulator (ralgds) is the binding partner of oog1. coimmunoprecipitation assay confirmed the interaction between oog1 and ralgds proteins. colo ... | 2006 | 16580637 |
| chmp5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis. | charged mvb protein 5 (chmp5) is a coiled coil protein homologous to the yeast vps60/mos10 gene and other escrt-iii complex members, although its precise function in either yeast or mammalian cells is unknown. we deleted the chmp5 gene in mice, resulting in a phenotype of early embryonic lethality, reflecting defective late endosome function and dysregulation of signal transduction. chmp5-/- cells exhibit enlarged late endosomal compartments that contain abundant internal vesicles expressing pro ... | 2006 | 16567502 |
| transport characteristics of mammalian rh and rh glycoproteins expressed in heterologous systems. | the development and use of heterologous expression systems is critical for deciphering the function of mammalian rh and rh-glycoproteins. the studies here use xenopus oocytes, well known for their ability to readily traffic and express difficult membrane proteins, and s. cerevisiae wild-type strains and mutants that are defective in ammonium transport. data obtained in both of these expression systems revealed that mammalian rh-glycoprotein-mediated transport (rhag, rhbg, and rhcg) is an electro ... | 2006 | 16563829 |
| deletion of the cabig1 gene reduces beta-1,6-glucan synthesis, filamentation, adhesion, and virulence in candida albicans. | the human fungal pathogen candida albicans is able to change its shape in response to various environmental signals. we analyzed the c. albicans big1 homolog, which might be involved in beta-1,6-glucan biosynthesis in saccharomyces cerevisiae. c. albicans big1 is a functional homolog of an s. cerevisiae big1 gene, because the slow growth of an s. cerevisiae big1 mutant was restored by introduction of c. albicans big1. cabig1p was expressed constitutively in both the yeast and hyphal forms. a spe ... | 2006 | 16552067 |
| analysis of transitions at two-fold redundant sites in mammalian genomes. transition redundant approach-to-equilibrium (trex) distance metrics. | the exchange of nucleotides at synonymous sites in a gene encoding a protein is believed to have little impact on the fitness of a host organism. this should be especially true for synonymous transitions, where a pyrimidine nucleotide is replaced by another pyrimidine, or a purine is replaced by another purine. this suggests that transition redundant exchange (trex) processes at the third position of conserved two-fold codon systems might offer the best approximation for a neutral molecular cloc ... | 2006 | 16545144 |
| mutations in sox2 cause anophthalmia-esophageal-genital (aeg) syndrome. | we report heterozygous, loss-of-function sox2 mutations in three unrelated individuals with anophthalmia-esophageal-genital (aeg) syndrome. one previously reported case [rogers, r.c. (1988) unknown cases. proceedings of the greenwood genetic center. 7, 57.] has a 2.7 mb deletion encompassing sox2 and associated with a cryptic translocation t(3;7)(q28;p21.3). the deletion and translocation breakpoints on chromosome 3q are >8.6 mb apart and both chromosome rearrangements have occurred de novo. ano ... | 2006 | 16543359 |
| structures of eukaryotic ribonucleotide reductase i define gemcitabine diphosphate binding and subunit assembly. | ribonucleotide reductase (rnr) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. crucial for rapidly dividing cells, rnr is a target for cancer therapy. in eukaryotes, rnr comprises a heterooligomer of alpha(2) and beta(2) subunits. rnr1, the alpha subunit, contains regulatory and catalytic sites; rnr2, the beta subunit (in yeast, a heterodimer of rnr2 and rnr4), houses the diferric-tyrosyl radical crucial for catalysis. here, we present three x-ray structures ... | 2006 | 16537480 |
| separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression. | separase is a protease whose liberation from its inhibitory chaperone securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit. we have created conditional knockout alleles of the mouse separase and securin genes. deletion of both copies of separase but not securin causes embryonic lethality. loss of securin reduces separase activity because deletion of just one copy of the separase gene is lethal to embryos lacking securin. in embryonic fibr ... | 2006 | 16533945 |
| targeting of c-terminal binding protein (ctbp) by arf results in p53-independent apoptosis. | arf encodes a potent tumor suppressor that antagonizes mdm2, a negative regulator of p53. arf also suppresses the proliferation of cells lacking p53, and loss of arf in p53-null mice, compared with arf or p53 singly null mice, results in a broadened tumor spectrum and decreased tumor latency. to investigate the mechanism of p53-independent tumor suppression by arf, potential interacting proteins were identified by yeast two-hybrid screen. the antiapoptotic transcriptional corepressor c-terminal ... | 2006 | 16508011 |
| isolates of candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses. | three distinct isolates of candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. patterns of infection differed significantly between both yeasts and mouse strains. systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible cba/cah mice than in the resistant balb/c ... | 2006 | 16503182 |
| the murine dnali1 gene encodes a flagellar protein that interacts with the cytoplasmic dynein heavy chain 1. | axonemal dyneins are large motor protein complexes generating the force for the movement of eukaryotic cilia and flagella. disruption of axonemal dynein function leads to loss of ciliary motility and can result in male infertility or lateralization defects. here, we report the molecular analysis of a murine gene encoding the dynein axonemal light intermediate chain dnali1. the dnali1 gene is localized on chromosome 4 and consists of six exons. it is predominantly expressed within the testis but ... | 2006 | 16496424 |
| regulation of cytoplasmic dynein atpase by lis1. | mutations in lis1 cause classical lissencephaly, a developmental brain abnormality characterized by defects in neuronal positioning. over the last decade, a clear link has been forged between lis1 and the microtubule motor cytoplasmic dynein. substantial evidence indicates that lis1 functions in a highly conserved pathway with dynein to regulate neuronal migration and other motile events. yeast two-hybrid studies predict that lis1 binds directly to dynein heavy chains (sasaki et al., 2000; tai e ... | 2006 | 16481446 |
| functional properties of the titin/connectin-associated proteins, the muscle-specific ring finger proteins (murfs), in striated muscle. | the efficient functioning of striated muscle is dependent upon the proper alignment and coordinated activities of several cytoskeletal networks including myofibrils, microtubules, and intermediate filaments. however, the exact molecular mechanisms dictating their cooperation and contributions during muscle differentiation and maintenance remain unknown. recently, the muscle specific ring finger (murf) family members have established themselves as excellent candidates for linking myofibril compon ... | 2005 | 16477476 |
| paracoccin, a glcnac-binding lectin from paracoccidioides brasiliensis, binds to laminin and induces tnf-alpha production by macrophages. | paracoccidioides brasiliensis components interact with host cells and can influence the pathogenesis of paracoccidioidomycosis (pcm). among the components released by p. brasiliensis, gp 43 and a heavily glycosylated antigen with mm>160 kda are the most recognized by serum antibodies from patients with pcm. in order to isolate the high mm glycoconjugate, we carried out affinity chromatography of a crude exoantigen preparation on immobilized jacalin. the bound fraction (jbe, jacalin binding exoan ... | 2006 | 16476564 |
| physical and functional interaction of noc2/rab3 in exocytosis. | rab, monomeric small ras-like gtpase, regulates intracellular membrane trafficking in eukaryotic cells. rab3 is involved in the exocytotic process in a variety of secretory cells including neuronal, neuroendocrine, endocrine, and exocrine cells. noc2, originally identified as a molecule homologous to rabphilin-3, is a putative effector of rab3. noc2 interacts with the active (gtp-bound) form of rab3 and regulates hormone secretion in neuroendocrine and endocrine cells and enzyme release in exocr ... | 2005 | 16473607 |
| formin proteins: purification and measurement of effects on actin assembly. | we describe methods for expressing and isolating formin proteins from a wide range of species and comparing quantitatively their effects on actin assembly. we first developed these procedures for purification of s. cerevisiae formins bni1 and bnr1 but have extended them to mammalian formins, including mouse mdia1 and mdia2 and human daam1. thus, the approach we describe should be universally applicable to the purification and analysis of formins from any eukaryote. formins expressed in yeast rat ... | 2006 | 16472660 |
| the effects of oral cardax (disodium disuccinate astaxanthin) on multiple independent oxidative stress markers in a mouse peritoneal inflammation model: influence on 5-lipoxygenase in vitro and in vivo. | disodium disuccinate astaxanthin ('rac'-dast; cardax) is a water-dispersible c40 carotenoid derivative under development for oral and parenteral administration for cardioprotection of the at-risk ischemic cardiovascular patient. in experimental infarction models in animals (rats, rabbits, and dogs), significant myocardial salvage has been obtained, up to 100% at the appropriate dose in dogs. the documented mechanism of action in vitro includes direct scavenging of biologically produced superoxid ... | 2006 | 16466747 |
| long inverted repeats in eukaryotic genomes: recombinogenic motifs determine genomic plasticity. | inverted repeats are unstable motifs in a genome, having a causal relation to fragment rearrangements and recombination events. we have investigated long inverted repeats (lir) of > 30 bp in length in eukaryotic genomes to assess their contribution to genome stability. an algorithm was first designed for searching for lirs with < 2 kb internal spacers and >85% identity (degree of homology between repeat copies of a lir). there are much fewer lirs in yeast, fruitfly, pufferfish and chicken than i ... | 2006 | 16466723 |
| p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation. | p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. therefore, we evaluated the effect of p205 on the p53 and rb-dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro in a p53-dependent manner. in addition, p205 induces increased expression of rb, and binds directly ... | 2006 | 16458891 |
| p19ras interacts with and activates p73 by involving the mdm2 protein. | p73beta is a structural and functional homologue of p53, a tumor suppressor gene. in this study, we identified a novel p73beta-binding protein, p19ras, by the yeast two-hybrid screening method. alternative splicing of the proto-oncogene h-ras pre-mrna has led to two distinct transcripts, p19ras and p21ras. in both endogenous and overexpressed systems, we confirmed that p19ras binds to full-length p73beta in vivo and in vitro. coexpression of p19ras with p73beta stimulated the transcriptional act ... | 2006 | 16436381 |
| evolutionary origins of the endocannabinoid system. | endocannabinoid system evolution was estimated by searching for functional orthologs in the genomes of twelve phylogenetically diverse organisms: homo sapiens, mus musculus, takifugu rubripes, ciona intestinalis, caenorhabditis elegans, drosophila melanogaster, saccharomyces cerevisiae, arabidopsis thaliana, plasmodium falciparum, tetrahymena thermophila, archaeoglobus fulgidus, and mycobacterium tuberculosis. sequences similar to human endocannabinoid exon sequences were derived from filtered b ... | 2006 | 16434153 |
| mouse ache binds in vivo to domain iv of laminin-1beta. | functions of acetylcholinesterase (ache) other than hydrolysis of acetylcholine, e.g. related to cell differentiation, synaptogenesis, neuronal signaling and diseases are well documented, but mechanisms supporting them are not understood. therefore, we searched for ache ligands in the central nervous system using a yeast two-hybrid screen (y2h). 18 independent candidates were identified. one of the membrane or extracellular proteins was laminin-1, an extracellular matrix protein involved in neur ... | 2005 | 16429555 |
| role of afr1, an abc transporter-encoding gene, in the in vivo response to fluconazole and virulence of cryptococcus neoformans. | we have recently demonstrated that upregulation of the atp binding cassette (abc) transporter-encoding gene afr1 in cryptococcus neoformans is involved in the in vitro resistance to fluconazole of this yeast. in the present study, we investigated the role of afr1 in the in vivo response to fluconazole in a mouse model of systemic cryptococcosis. mice were infected with a wild-type fluconazole-susceptible strain of c. neoformans, strain bpy22; an afr1 mutant, bpy444, which displayed hypersuscepti ... | 2006 | 16428784 |
| the carbohydrate-recognition domain of dectin-2 is a c-type lectin with specificity for high mannose. | we examined the carbohydrate-binding potential of the c-type lectin-like receptor dectin-2 (clecf4n). the carbohydrate-recognition domain (crd) of dectin-2 exhibited cation-dependent mannose/fucose-like lectin activity, with an ic(50) for mannose of approximately 20 mm compared to an ic(50) of 1.5 mm for the macrophage mannose receptor when assayed by similar methodology. the extracellular domain of dectin-2 exhibited binding to live candida albicans and the saccharomyces-derived particle zymosa ... | 2006 | 16423983 |
| candida albicans ecm33p is important for normal cell wall architecture and interactions with host cells. | candida albicans ecm33 encodes a glycosylphosphatidylinositol-linked cell wall protein that is important for cell wall integrity. it is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis. to identify potential mechanisms through which ecm33p contributes to virulence, we investigated the interactions of c. albicans ecm33delta mutants with endothelial cells and the fadu oral epithelial cell line in vitro. the growth rate of blastospores of strains cont ... | 2006 | 16400176 |
| dj-1 interacts with hipk1 and affects h2o2-induced cell death. | dj-1 is a novel oncogene and causative gene for the familial form of parkinson's disease (pd). dj-1 has multiple functions, including anti-oxidative stress by eliminating reactive oxygen species (ros) and transcriptional regulation as a coactivator, and loss of these functions are thought to trigger the onset of pd. the mechanism underlying the prevention of cell death by dj-1 is, however, not clear. in this study, we found that dj-1 directly bound to homeodomaininteracting protein kinase 1 (hip ... | 2006 | 16390825 |
| a computational screen for mammalian pseudouridylation guide h/aca rnas. | the box h/aca rna gene family is one of the largest non-protein-coding gene families in eukaryotes and archaea. recently, we developed snogps, a computational screening program for h/aca snornas, and applied it to saccharomyces cerevisiae. we report here results of extending our method to screen for h/aca rnas in multiple large genomes of related species, and apply it to the human, mouse, and rat genomes. because of the 250-fold larger search space compared to s. cerevisiae, significant enhancem ... | 2006 | 16373490 |
| new insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium. | members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. we have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1b, 4.1r and 4.1n, in mouse kidney. we describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidn ... | 2006 | 16368544 |
| rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. | the rad9 gene is evolutionarily conserved. analysis of the gene from yeast, mouse and human reveal roles in multiple, fundamental biological processes primarily but not exclusively important for regulating genomic integrity. the encoded mammalian proteins participate in promoting resistance to dna damage, cell cycle checkpoint control, dna repair, and apoptosis. other functions include a role in embryogenesis, the transactivation of multiple target genes, co-repression of androgen-induced transc ... | 2006 | 16365875 |
| from an inborn error patient to a search for regulatory meaning: a biotin conducted voyage. | this article summarizes some findings of a research that i have pursued for the past 25 years, whose roots are immersed in the field of inherited metabolic disorders, and deal with different aspects of the vitamin biotin, starting with a patient with multiple carboxylase deficiency (mcd). several of mcd clinical manifestations resemble those of infant malnutrition; we demonstrated that about one-third of infants with this common nutritional disorder were indeed biotin-deficient, and that this de ... | 2006 | 16359899 |
| new phenotypes of functional expression of the mkir2.1 channel in potassium efflux-deficient saccharomyces cerevisiae strains. | the functional expression of the mouse kir2.1 potassium channel in yeast cells lacking transport systems for potassium and sodium efflux (ena1-4delta nha1delta) resulted in increased cell sensitivity to high external concentrations of potassium. the phenotype depended on the level of kir2.1 expression and on the external ph. the activity of kir2.1p in the yeast cells was almost negligible at ph 3.0 and the highest at ph 7.0. kir2.1p was permeable for both potassium and rubidium cations, but neit ... | 2005 | 16358319 |
| the rad50s allele promotes atm-dependent dna damage responses and suppresses atm deficiency: implications for the mre11 complex as a dna damage sensor. | genetic and cytologic data from saccharomyces cerevisiae and mammals implicate the mre11 complex, consisting of mre11, rad50, and nbs1, as a sensor of dna damage, and indicate that the complex influences the activity of ataxia-telangiectasia mutated (atm) in the dna damage response. rad50(s/s) mice exhibit precipitous apoptotic attrition of hematopoietic cells. we generated atm- and chk2-deficient rad50(s/s) mice and found that rad50(s/s) cellular attrition was strongly atm and chk2 dependent. t ... | 2005 | 16357220 |
| do alix and alg-2 really control endosomes for better or for worse? | alix/aip1 (alg-2-interacting protein x/apoptosis-linked-gene-2-interacting protein 1) is an adaptor protein that was first described for its capacity to bind to the calcium-binding protein alg-2 (apoptosis-linked gene 2), the expression of which seemed necessary for cell death. over-expression of truncated forms of alix blocks caspase-dependent and -independent mechanisms of cell death. numerous observations in yeast and in mammalian cells suggest that alix controls the making of and trafficking ... | 2006 | 16354163 |
| possible role of mouse poly(a) polymerase mgld-2 during oocyte maturation. | cytoplasmic polyadenylation of mrnas is involved in post-transcriptional regulation of genes, including translational activation. in addition to yeast cid1 and cid13 and mouse tpap, gld-2 has been recently identified as a cytoplasmic poly(a) polymerase in caenorhabditis elegans and xenopus oocytes. in this study, we have characterized mouse gld-2, mgld-2, in adult tissues, meiotically maturing oocytes, and nih3t3 cultured cells. mgld-2 was ubiquitously present in all tissues and cells tested. mg ... | 2006 | 16325797 |
| the role of transcriptional coactivator trap220 in myelomonocytic differentiation. | the trap220 subunit of the thyroid hormone receptor-associated polypeptide transcription coactivator complex (trap/mediator complex), mammalian counterpart of the yeast mediator complex, is proposed to act on a variety of major and specific biological events through physical interactions with nuclear receptors. the vitamin d receptor (vdr) and retinoic acid receptor (rar), coupled with retinoid x receptor (rxr), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, ... | 2005 | 16324150 |
| mammalian e4 is required for cardiac development and maintenance of the nervous system. | ubiquitin conjugation typically requires three classes of enzyme: e1, e2, and e3. a fourth type of enzyme (e4), however, was recently shown to be required for the degradation of certain types of substrate in yeast. we previously identified ufd2a (also known as e4b) as an e4 in mammals. ufd2a is exclusively expressed in cardiac muscle during mouse embryonic development, but it is abundant in neurons of adult mice and is implicated in the pathogenesis of neurodegenerative disease. the precise phys ... | 2005 | 16314518 |
| amyloid precursor proteins anchor cpeb to membranes and promote polyadenylation-induced translation. | the cytoplasmic polyadenylation element (cpe) binding factor, cpeb, is a sequence-specific rna binding protein that controls polyadenylation-induced translation in germ cells and at postsynaptic sites of neurons. a yeast two-hybrid screen with a mouse brain cdna library identified the transmembrane amyloid precursor-like protein 1 (aplp1) as a cpeb-interacting factor. cpeb binds the small intracellular domain (icd) of aplp1 and the related proteins aplp2 and app. these proteins promote polyadeny ... | 2005 | 16314516 |
| an autoregulatory loop controlling orphan nuclear receptor dax-1 gene expression by orphan nuclear receptor errgamma. | the estrogen receptor-related receptor gamma (errgamma/err3/nr3b3) is a member of the nuclear receptor superfamily that activates transcription in the absence of ligand. however, the detailed mechanism of gene regulation by errgamma is not fully understood. in this study we have found that the orphan nuclear receptor errgamma activates the dax-1 promoter, which, in turn, represses transactivation by errgamma. serial deletions of mouse dax-1 (mdax-1) gene promoter have revealed that the region re ... | 2005 | 16314306 |
| transcriptional activity of pax3 is co-activated by taz. | pax3 is a transcription factor which functions in embryonic development and human diseases. in a yeast two-hybrid screen with full-length pax3 as bait, we isolated a clone encoding transcriptional co-activator with pdz-binding motif (taz) from an e10.5 mouse embryo cdna library. co-immunoprecipitation and nuclear co-localization of taz with pax3 suggest that their association is functionally relevant. in situ hybridization revealed taz and pax3 expression to partially overlap in the paraxial mes ... | 2006 | 16300735 |
| iron metabolism mutant hbd mice have a deletion in sec15l1, which has homology to a yeast gene for vesicle docking. | defects in iron absorption and utilization lead to iron deficiency and anemia. while iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. we undertook a positional cloning project to identify the causative mutation for the hemoglobin-deficit (hbd) mouse mutant, which suffers from a microcytic, hypochromic anemia apparently due to defective iron transport ... | 2005 | 16289749 |
| a novel nucleolar protein interacts with ribosomal protein s19. | the gene encoding ribosomal protein s19 (rps19) is mutated in approximately 25% of patients with diamond-blackfan anemia (dba), which is a rare congenital erythroblastopenia. dba patients have a variety of clinical characteristics, and the role of the rps19 gene in the pathogenesis of the disease is presently unknown. to investigate a possible role for rps19 in erythropoiesis, we looked for proteins associated with mouse rps19 using a yeast two-hybrid system and identified a novel protein, which ... | 2006 | 16289379 |
| psf1 is essential for early embryogenesis in mice. | psf1 (partner of sld five 1) forms a novel heterotetramer complex, gins (go, ichi, nii, and san; five, one, two, and three, respectively, in japanese), with sld5, psf2, and psf3. the formation of this complex is essential for the initiation of dna replication in yeast and xenopus laevis egg extracts. although all of the components are well conserved in higher eukaryotes, the biological function in vivo is largely unknown. we originally cloned the mouse ortholog of psf1 from a hematopoietic stem ... | 2005 | 16287864 |
| the enigmatic role of sir2 in aging. | in this issue of cell, longo and colleagues (fabrizio et al., 2005) examine the role of sir2, a histone deacetylase, in chronological aging in yeast by measuring the long-term survival of nondividing cells. in contrast to measurements of aging for mitotic cells, cell survival in the nonmitotic state is decreased by sir2 activity under conditions that mimic calorie restriction. | 2005 | 16286003 |
| redox-dependent transcriptional regulation. | reactive oxygen species contribute to the pathogenesis of a number of disparate disorders including tissue inflammation, heart failure, hypertension, and atherosclerosis. in response to oxidative stress, cells activate expression of a number of genes, including those required for the detoxification of reactive molecules as well as for the repair and maintenance of cellular homeostasis. in many cases, these induced genes are regulated by transcription factors whose structure, subcellular localiza ... | 2005 | 16284189 |
| interaction of mouse pem protein and cell division cycle 37 homolog. | mouse pem, a homeobox gene, encodes a protein consisting of 210 amino acid residues. to study the function of mouse pem protein, we used the yeast two-hybrid system to screen the library of 7-day mouse embryo with full-length mouse pem cdna. fifty-two colonies were obtained after 1.57 x 10(8) colonies were screened by nutrition limitation and beta-galactosidase assay. seven individual insert fragments were obtained from the library, and three of them were identified, one of which was confirmed t ... | 2005 | 16270159 |
| identification and characterization of novel igfbp5 interacting protein: evidence igfbp5-ip is a potential regulator of osteoblast cell proliferation. | insulin-like growth factor binding protein-5 (igfbp5) is a multifunctional protein, which acts not only as a traditional binding protein, but also functions as a growth factor independent of igfs to stimulate bone formation. it has been predicted that the intrinsic growth factor action of igfbp5 involves binding of igfbp5 to a putative receptor to induce downstream signaling pathways and/or nuclear translocation of igfbp5 to influence transcription of genes involved in osteoblast cell proliferat ... | 2006 | 16269403 |
| glucose as a regulator of eukaryotic gene transcription. | glucose has essential metabolic roles as both a fuel for energy and a substrate for the biosynthesis of cell components. because of its central importance, many cells have evolved mechanisms to sense glucose levels in their environment and to adapt the expression of their genetic information to glucose availability. this glucose signaling is vital in mammalian cells where derangements in glucose utilization might contribute to conditions such as obesity and type 2 diabetes. two crucial issues st ... | 2005 | 16269245 |
| the flo8 transcription factor is essential for hyphal development and virulence in candida albicans. | the transcription factor flo8 is essential for filamentous growth in saccharomyces cerevisiae and is regulated under the camp/protein kinase a (pka) pathway. to determine whether a similar pathway/regulation exists in candida albicans, we have cloned c. albicans flo8 by its ability to complement s. cerevisiae flo8. deleting flo8 in c. albicans blocked hyphal development and hypha-specific gene expression. the flo8/flo8 mutant is avirulent in a mouse model of systemic infection. genome-wide trans ... | 2006 | 16267276 |
| obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast. | storage and degradation of triglycerides are essential processes to ensure energy homeostasis and availability of precursors for membrane lipid synthesis. recent evidence suggests that an emerging class of enzymes containing a conserved patatin domain are centrally important players in lipid degradation. here we describe the identification and characterization of a major triglyceride lipase of the adipose triglyceride lipase/brummer family, tgl4, in the yeast saccharomyces cerevisiae. eliminatio ... | 2006 | 16267052 |
| mycobacterium tuberculosis lipoarabinomannan-mediated irak-m induction negatively regulates toll-like receptor-dependent interleukin-12 p40 production in macrophages. | mannose-capped lipoarabinomannans (man-lams) are members of the repertoire of mycobacterium tuberculosis modulins that the bacillus uses to subvert the host innate immune response. interleukin-12 (il-12) production is critical for mounting an effective immune response by the host against m. tuberculosis. we demonstrate that man-lam inhibits il-12 p40 production mediated by subsequent challenge with lipopolysaccharide (lps). man-lam inhibits lps-induced il-12 p40 expression in an il-10-independen ... | 2005 | 16263713 |
| isolation and characterization of a transcriptional cofactor and its novel isoform that bind the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-gamma. | using the dna-binding domain (dbd) and hinge region of human peroxisome proliferator-activated receptor (ppar)-gamma as bait in yeast two-hybrid screen, we isolated partial cdna identical with that of the c terminal of kiaa1769. kiaa1769 encodes a 2080-amino acid protein (molecular mass, 231 kda) that was recently identified to interact with pparalpha and termed pparalpha-interacting cofactor 285 (here referred to as ppargamma-dbd-interacting protein 1 (pdip1)-alpha). pdip1 mrna was expressed in ... | 2006 | 16239304 |
| frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. | deficiency of the frataxin mrna alters the transcriptome, triggering neuro- and cardiodegeneration in friedreich's ataxia. we microarrayed murine frataxin-deficient heart tissue, liver tissue and cardiocytes and observed a transcript down-regulation to up-regulation ratio of nearly 2:1 with a mitochondrial localization of transcriptional changes. combining all mouse and human microarray data for frataxin-deficient cells and tissues, the most consistently decreased transcripts were mitochondrial ... | 2005 | 16239244 |
| the m-aaa protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. | aaa proteases comprise a conserved family of membrane bound atp-dependent proteases that ensures the quality control of mitochondrial inner-membrane proteins. inactivation of aaa proteases causes pleiotropic phenotypes in various organisms, including respiratory deficiencies, mitochondrial morphology defects, and axonal degeneration in hereditary spastic paraplegia (hsp). the molecular basis of these defects, however, remained unclear. here, we describe a regulatory role of an aaa protease for m ... | 2005 | 16239145 |
| the atpase motif in rad51d is required for resistance to dna interstrand crosslinking agents and interaction with rad51c. | homologous recombination (hr) is a mechanism for repairing dna interstrand crosslinks and double-strand breaks. in mammals, hr requires the activities of the rad51 family (rad51, rad51b, rad51c, rad51d, xrcc2, xrcc3 and dmc1), each of which contains conserved atp binding sequences (walker motifs a and b). rad51d is a dna-stimulated atpase that interacts directly with rad51c and xrcc2. to test the hypothesis that atp binding and hydrolysis by rad51d are required for the repair of interstrand cros ... | 2005 | 16236763 |
| identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. | the reduction of iron is an essential step in the transferrin (tf) cycle, which is the dominant pathway for iron uptake by red blood cell precursors. a deficiency in iron acquisition by red blood cells leads to hypochromic, microcytic anemia. using a positional cloning strategy, we identified a gene, six-transmembrane epithelial antigen of the prostate 3 (steap3), responsible for the iron deficiency anemia in the mouse mutant nm1054. steap3 is expressed highly in hematopoietic tissues, colocaliz ... | 2005 | 16227996 |
| the mouse sphingomyelin synthase 1 (sms1) gene is alternatively spliced to yield multiple transcripts and proteins. | sphingomyelin synthase 1 (sms1) is a recently identified 413-residue protein that plays a critical role in sphingolipid metabolism by catalyzing the conversion of ceramide and phosphatidylcholine to sphingomyelin and diacylglycerol (dag). we have previously reported the isolation of a mouse sms1 encoding cdna that contains a unique 5' utr sequence. three other mouse sms1 cdnas that differed in their 5' and 3' non-coding sequences were present in genbank. in order to ascertain the origin of the u ... | 2005 | 16226406 |
| mammalian smaug is a translational repressor that forms cytoplasmic foci similar to stress granules. | cytoplasmic events depending on rna-binding proteins contribute to the fine-tuning of gene expression. sterile alpha motif-containing rna-binding proteins constitute a novel family of post-transcriptional regulators that recognize a specific rna sequence motif known as smaug recognition element (sre). the drosophila member of this family, dsmaug, triggers the translational repression and deadenylation of maternal mrnas by independent mechanisms, and the yeast homologue vts1 stimulates degradatio ... | 2005 | 16221671 |
| wox1 is essential for tumor necrosis factor-, uv light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. | ww domain-containing oxidoreductase wox1, also named wwox or for, undergoes tyr33 phosphorylation at its first n-terminal ww domain and subsequent nuclear translocation in response to sex steroid hormones and stress stimuli. the activated wox1 binds tumor suppressor p53, and both proteins may induce apoptosis synergistically. functional suppression of wox1 by antisense mrna or a dominant negative abolishes p53-mediated apoptosis. here, we determined that uv light, anisomycin, etoposide, and hypo ... | 2005 | 16219768 |