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diversity of trna genes in eukaryotes.we compare the diversity of chromosomal-encoded transfer rna (trna) genes from 11 eukaryotes as identified by trnascan-se of their respective genomes. they include the budding and fission yeast, worm, fruit fly, fugu, chicken, dog, rat, mouse, chimp and human. the number of trna genes are between 170 and 570 and the number of trna isoacceptors range from 41 to 55. unexpectedly, the number of trna genes having the same anticodon but different sequences elsewhere in the trna body (defined here as ...200617088292
ubiquitin receptor proteins hhr23a and hplic2 interact.ubiquitin receptor proteins play an important role in delivering ubiquitylated protein substrates to the proteasome for degradation. hhr23a and hplic2 are two such ubiquitin receptors that contain ubiquitin-like (ubl) domains, which interact with the proteasome, and ubiquitin-associated (uba) domains, which interact with ubiquitin. depending on their abundance ubl/uba family members can either promote or inhibit the degradation of other proteins, which suggests their participation in the deliver ...200717098253
esldb: eukaryotic subcellular localization database.eukaryotic subcellular localization database collects the annotations of subcellular localization of eukaryotic proteomes. so far five proteomes have been processed and stored: homo sapiens, mus musculus, caenorhabditis elegans, saccharomyces cerevisiae and arabidopsis thaliana. for each sequence, the database lists localization obtained adopting three different approaches: (i) experimentally determined (when available); (ii) homology-based (when possible); and (iii) predicted. the latter is com ...200717108361
conditional stimulation of type v and vi adenylyl cyclases by g protein betagamma subunits.in a yeast two-hybrid screen of mouse brain cdna library, using the n-terminal region of human type v adenylyl cyclase (hacv) as bait, we identified g protein beta2 subunit as an interacting partner. additional yeast two-hybrid assays showed that the gbeta(1) subunit also interacts with the n-terminal segments of hacv and human type vi adenylyl cyclase (hacvi). in vitro adenylyl cyclase (ac) activity assays using membranes of sf9 cells expressing hacv or hacvi showed that gbetagamma subunits enh ...200717110384
murine pif1 interacts with telomerase and is dispensable for telomere function in vivo.pif1 is a 5'-to-3' dna helicase critical to dna replication and telomere length maintenance in the budding yeast saccharomyces cerevisiae. scpif1 is a negative regulator of telomeric repeat synthesis by telomerase, and recombinant scpif1 promotes the dissociation of the telomerase rna template from telomeric dna in vitro. in order to dissect the role of mpif1 in mammals, we cloned and disrupted the mpif1 gene. in wild-type animals, mpif1 expression was detected only in embryonic and hematopoieti ...200717130244
use of the porcine intestinal epithelium (pie)-assay to analyze early stages of colonization by the human fungal pathogen candida albicans.virulence of c. albicans strains can be tested using a mouse model of haematogenously disseminated candida cells. initial steps of host-pathogen contact such as adhesion and colonization are not taken into account due to the injection of candida cells into the blood stream. here we describe an assay, based on the ex vivo usage of porcine intestinal epithelium (pie), that is useful to monitor the early stages of a c. albicans infection. the ability of c. albicans to undergo morphogenetic switchin ...200617139615
mammalian timeless and tipin are evolutionarily conserved replication fork-associated factors.the function of the mammalian timeless protein (tim) has been enigmatic. tim is essential for early embryonic development, but little is known regarding its biochemical and cellular function. although identified based on similarity to a drosophila circadian clock factor, it also shares similarity with a second family of proteins that is more widely conserved throughout eukaryotes. members of this second protein family in yeast (s.c. tof1p, s.p. swi1p) have been implicated in dna synthesis, s-pha ...200717141802
alpha-synuclein, oxidative stress and apoptosis from the perspective of a yeast model of parkinson's disease.the neuronal protein alpha-synuclein (alpha-syn) has been suggested to be one of the factors linked to parkinson's disease (pd). several organisms, including the rat, mouse, worm, and fruit fly, are being used to study alpha-syn pathobiology. a new model organism was recently added to this armamentarium: the budding yeast saccharomyces cerevisiae. the yeast system recapitulates many of the findings made with higher eukaryotes. for example, yeast cells expressing alpha-syn accumulate lipid drople ...200617156009
regulation of protein tyrosine phosphatase 1b by sumoylation.protein-tyrosine phosphatase 1b (ptp1b) is an ubiquitously expressed enzyme that negatively regulates growth-factor signalling and cell proliferation by binding to and dephosphorylating key receptor tyrosine kinases, such as the insulin receptor. it is unclear how the activity of ptp1b is regulated. using a yeast two-hybrid assay, a protein inhibitor of activated stat1 (pias1) was isolated as a ptp1b-interacting protein. here, we show that pias1, which functions as a small ubiquitin-like modifie ...200717159996
inhibition of cdc2/cyclin b1 in response to selenium-induced oxidative stress during spermatogenesis: potential role of cdc25c and p21.various cell cycle regulators control and coordinate the process of cell cycle. because of the crucial involvement of cdc2, cyclin b1, cdc25c, and p21 in cell cycle regulation, the present study was aimed to investigate the possibility that selenium (se)-induced oxidative stress mediated alterations in cdc25c and p21 may cause modulations in the cdc2/cyclin b1 complex responsible for g2/m phase checkpoint during meiosis i of spermatogenesis. to create different se status-deficient, adequate and ...200717160696
differential regulation of splicing, localization and stability of mammalian ard1235 and ard1225 isoforms.ard1 protein is a mammalian gene product homologous to a yeast ard1p (arrest defective 1 protein) acetyltransferase. although two alternative splicing products of ard1, ard1(235) and ard1(225), were reported in mouse, only ard1(235) orthologue was reported in humans. here we show that ard1(225) is not expressed in humans, suggesting that factors regulating alternative splicing of ard1 may have evolved differently between species. in human cells, hard1(235) is shown to be present in both nucleus ...200717161380
the wilms tumour suppressor protein wt1 (+kts isoform) binds alpha-actinin 1 mrna via its zinc-finger domain.mutations in wt1 are associated with developmental syndromes that affect the urogenital system and neoplasms, including wilms tumour, acute myeloid leukemia, and breast and prostate cancers. the wt1 protein belongs to the early growth response family of zinc-finger transcription factors. uniquely to wt1, an evolutionarily conserved alternative splice event inserts the tripeptide kts, between zinc fingers 3 and 4. whereas -kts isoforms bind dna and activate or repress transcription, +kts isoforms ...200617167543
perturbation of the activity of replication origin by meiosis-specific transcription.we have determined the activity of all arss on the saccharomyces cerevisiae chromosome vi as chromosomal replication origins in premeiotic s-phase by neutral/neutral two-dimensional gel electrophoresis. the comparison of origin activity of each origin in mitotic and premeiotic s-phase showed that one of the most efficient origins in mitotic s-phase, ars605, was completely inhibited in premeiotic s-phase. ars605 is located within the open reading frame of msh4 gene that is transcribed specificall ...200717170106
protein inhibitor of activated stat1 interacts with and up-regulates activities of the pro-proliferative transcription factor krüppel-like factor 5.krüppel-like factor 5 (klf5) is a zinc finger-containing transcription factor that regulates proliferation of various cell types, including fibroblasts, smooth muscle cells, and intestinal epithelial cells. to identify proteins that interact with klf5, we performed a yeast two-hybrid screen of a 17-day mouse embryo cdna library with klf5 as bait. the screen revealed 21 preys clustered in four groups as follows: proteins mediating gene expression, metabolism, trafficking, and signaling. among the ...200717178721
antimicrobial and cytotoxic knotwood extracts and related pure compounds and their effects on food-associated microorganisms.knotwood or bark extracts prepared from 30 species of hard and soft wood trees as well as selected pure compounds (lignans, stilbenes and flavonoids) were assayed for their antimicrobial activity against a battery of both gram positive and negative bacteria, yeasts, and filamentous fungi (bacillus cereus, staphylococcus aureus, listeria monocytogenes, lactobacillus plantarum, escherichia coli, salmonella infantis, pseudomonas fluorescens, candida albicans, saccharomyces cerevisiae, aspergillus f ...200717188387
expression of cre recombinase in dopaminoceptive neurons.dopamine-activated signaling regulates locomotor and emotional responses and alterations in dopamine-signaling are responsible of several psychomotor disorders. in order to identify specific functions of these pathways, the cre/loxp system has been used. here, we describe the generation and the characterization of a transgenic mouse line expressing the cre recombinase in dopaminoceptive neurons. to this purpose, we used as expression vector a 140 kb yeast artificial chromosome (yac) containing t ...200717201924
dmp1 and tumor suppression.dmp1 (cyclin d binding myb-like protein 1; also called dmtf1) is a transcription factor that was isolated in a yeast two-hybrid screen through its binding property to cyclin d2. although it was initially predicted to be involved in the cyclin d-rb pathway, overexpression of dmp1 in primary cells induces cell cycle arrest in an arf, p53-dependent fashion. dmp1 is a unique arf regulator, the promoter of which is activated by oncogenic ras-raf signaling. dmp1 expression is repressed by physiologica ...200717237816
lower filamentation rates of candida dubliniensis contribute to its lower virulence in comparison with candida albicans.candida albicans and c. dubliniensis are very closely related yeast species. in this study, we have conducted a thorough comparison of the ability of the two species to produce hyphae and their virulence in two infection models. under all induction conditions tested c. albicans consistently produced hyphae more efficiently than c. dubliniensis. in the oral reconstituted human epithelial model, c. dubliniensis isolates grew exclusively in the yeast form, while the c. albicans strains produced abu ...200717251042
srg3 interacts directly with the major components of the swi/snf chromatin remodeling complex and protects them from proteasomal degradation.the mammalian swi/snf complex is an evolutionarily conserved atp-dependent chromatin remodeling complex that consists of nine or more components. srg3, a murine homologue of yeast swi3, drosophila moira, and human baf155, is a core component of the murine swi/snf complex required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. here we report that srg3 interacts directly with other components of the mammalian swi/snf comple ...200717255092
recognition of age-damaged (r,s)-adenosyl-l-methionine by two methyltransferases in the yeast saccharomyces cerevisiae.the biological methyl donor s-adenosylmethionine (adomet) can exist in two diastereoisomeric states with respect to its sulfonium ion. the s configuration, (s,s)-adomet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. under physiological conditions, however, the sulfonium ion can spontaneously racemize to the r form, producing (r,s)-adomet. as of yet, (r,s)-adomet has no known physiological function and may inhibit cel ...200717264075
high level expression of a promising anti-idiotypic antibody fragment vaccine against hiv-1 in pichia pastoris.we have expressed the anti-idiotypic antibody 3h6 fab directed against the hiv-1 broadly neutralising antibody 2f5 in methylotrophic yeast pichia pastoris. the chimeric human/mouse fab fragment was expressed under control of the inducible aox1 promoter and secreted via the alpha mating factor leader of saccharomyces cerevisiae. bioreactor experiments showed the ability of the recombinant p. pastoris clone to secrete up to 260 mg/l fab fragment in the culture supernatant during a five days cultiv ...200717270302
rna-p53 interactions in vitro.the tumor suppressor protein p53 is mutated in over half of human cancers. despite 25 years of study, the complex regulation of this protein remains unclear. after serendipitously detecting rna binding by p53 in the yeast three-hybrid system (y3h), we are exploring the specificity and function of this interaction. electrophoretic mobility shift assays show that full-length p53 binds equally to rnas that are strongly distinguished in the y3h. rna binding blocks sequence-specific dna binding by p5 ...200717288451
genotypic and physiological characterization of saccharomyces boulardii, the probiotic strain of saccharomyces cerevisiae.saccharomyces boulardii, a yeast that was isolated from fruit in indochina, has been used as a remedy for diarrhea since 1950 and is now a commercially available treatment throughout europe, africa, and south america. though initially classified as a separate species of saccharomyces, recent publications have shown that the genome of s. boulardii is so similar to saccharomyces cerevisiae that the two should be classified as conspecific. this raises the question of the distinguishing molecular an ...200717293506
molecular cloning and responsive expression to injury stimulus of a defender against cell death 1 (dad1) gene from bay scallops argopecten irradians.apoptosis is an active process of cell death, which is an integral part of growth and development in multicellular organisms. the defender against cell death 1 (dad1), the regulatory protein to inhibit the apoptosis process, was first cloned from the bay scallop argopecten irradians by randomly sequencing a whole tissue cdna library and rapid amplification of cdna end (race). the full-length cdna of the a. irradians dad1 was 607 bp, consist of a 5'-terminal untranslated region (utr) of 63 bp, a ...200817294251
lot6p from saccharomyces cerevisiae is a fmn-dependent reductase with a potential role in quinone detoxification.nad(p)h:quinone acceptor oxidoreductases are flavoenzymes expressed in the cytoplasm of many tissues and afford protection against the cytotoxic effects of electrophilic quinones by catalyzing a strict two-electron reduction. such enzymes have been reported from several mammalian sources, e.g. human, mouse and rat, and from plant species. here, we report identification of lot6p (ylr011wp), the first soluble quinone reductase from the unicellular model organism saccharomyces cerevisiae. localizat ...200717298444
hiv-tat protein transduction domain specifically attenuates growth of polyamine deprived tumor cells.polyamines are essential for tumor cell growth, and the polyamine pathway represents an attractive target for cancer treatment. several polyamine transport proteins have been cloned and characterized in bacteria and yeast cells; however, the mechanism of polyamine entry into mammalian cells remains poorly defined, although a role for proteoglycans has been suggested. here, we show that the hiv-tat transduction peptide, which is known to enter cells via a proteoglycan-dependent pathway, efficient ...200717308074
dietary selenium variation-induced oxidative stress modulates cdc2/cyclin b1 expression and apoptosis of germ cells in mice testis.oxidative stress has been linked with apoptosis in germ cells and with male infertility. however, the molecular mechanism of oxidative-stress-mediated apoptosis in germ cells has not been clearly defined so far. because of the involvement of cdc2 and cyclin b1 in cell cycle regulation and their plausible role in apoptosis, the present study aimed to investigate the possibility that selenium (se)-induced oxidative-stress-mediated modulations of these cell cycle regulators cause dna damage and apo ...200717320365
mammalian tumor suppressor int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pvhl-independent regulation.the hypoxia-inducible factors hif-1 alpha and hif-2 alpha are structurally similar as regards their dna-binding and dimerization domains, but differ in their transactivation domains and, as is shown by experiments using hif-1 alpha(-/-) and hif-2 alpha(-/-) mice, in their functions. this implies that hif-1 alpha and hif-2 alpha may have unique target genes. to address this discrepancy and identify hif-2 alpha-specific target genes, we performed yeast two-hybrid analysis and identified the tumor ...200717324924
characterization of a novel alternatively spliced human transcript encoding an n-terminally truncated vps24 protein that suppresses the effects of bax in an escrt independent manner in yeast.elucidating novel anti-apoptotic regulatory pathways is central to further understanding the molecular basis of several pathologies, including cancer. we have previously reported the identification of several mammalian cdnas effective in preventing the lethal effects of heterologous expression of a pro-apoptotic bax cdna in yeast [yang, z., khoury, c., jean-baptiste, g., greenwood, m.t., 2006. identification of mouse sphingomyelin synthase 1 (sms1) as a suppressor of bax mediated cell death in y ...200717331679
[conservation of the mc domains in eukaryotic termination factor erf3].eukaryotic translation termination employs two protein factors, erf1 and erf3. proteins of the erf3 family each consist of three domains. the n and m domains vary in different species, while the c domains are highly homologous. the mc domains of homo sapiens erf3a (hgspt i), xenopus laevis erf3 (xsup35), and mus musculus erf3a (mgspti) and erf3b (mgspt2) were found to compensate for the sup35-21(ts) temperature-sensitive mutation and lethal disruption of the sup35 gene in yeast saccharomyces cer ...200717333937
characterization of hampin/msl1 as a node in the nuclear interactome.hampin, homolog of drosophila msl1, is a partner of histone acetyltransferase myst1/mof. functions of these proteins remain poorly understood beyond their participation in chromatin remodeling complex msl. in order to identify new proteins interacting with hampin, we screened a mouse cdna library in yeast two-hybrid system with mouse hampin as bait and found five high-confidence interactors: myst1, tpr proteins ttc4 and kiaa0103, nop17 (homolog of a yeast nucleolar protein), and transcription fa ...200717335777
mammalian model hosts of cryptococcal infection.the rising incidence of serious fungal diseases represents a growing threat to human health. cryptococcus neoformans, an encapsulated yeast saprophyte with global distribution, has been recognized as an important emerging pathogen. humans frequently develop asymptomatic or mild infection with c. neoformans, but individuals with impaired host defense systems may develop severe pneumonia and potentially fatal meningoencephalitis. insight into the biology and virulence of c. neoformans is advancing ...200717348287
mouse homologue of yeast prp19 interacts with mouse sug1, the regulatory subunit of 26s proteasome.yeast prp19 has been shown to involve in pre-mrna splicing and dna repair as well as being an ubiquitin ligase. mammalian homologue of yeast prp19 also plays on similar functional activities in cells. in the present study, we isolated mouse sug1 (msug1) as binding partner of mouse prp19 (mprp19) by the yeast two-hybrid system. we confirmed the interaction of mprp9 with msug1 by gst pull-down assay and co-immunoprecipitation assay. the n-terminus of mprp19 including u-box domain was associated wi ...200717349974
essential gene identification and drug target prioritization in aspergillus fumigatus.aspergillus fumigatus is the most prevalent airborne filamentous fungal pathogen in humans, causing severe and often fatal invasive infections in immunocompromised patients. currently available antifungal drugs to treat invasive aspergillosis have limited modes of action, and few are safe and effective. to identify and prioritize antifungal drug targets, we have developed a conditional promoter replacement (cpr) strategy using the nitrogen-regulated a. fumigatus niia promoter (pniia). the gene e ...200717352532
a female-biased expressed elongase involved in long-chain hydrocarbon biosynthesis and courtship behavior in drosophila melanogaster.drosophila melanogaster produces sexually dimorphic cuticular pheromones that are a key component of the courtship behavior leading to copulation. these molecules are hydrocarbons, with lengths of 23 and 25 carbons in males (mainly with one double bond) and 27 and 29 carbons in females (mainly with two double bonds). here, we describe an elongase gene, elof, with female-biased expression. the 771-bp orf encodes a 257-aa protein that shows the highest sequence identity with mouse ssc1 elongase (3 ...200717360514
crystal structure of murine cstf-77: dimeric association and implications for polyadenylation of mrna precursors.cleavage stimulation factor (cstf) is a heterotrimeric protein complex essential for polyadenylation of mrna precursors. the 77 kda subunit, cstf-77, is known to mediate interactions with the other two subunits of cstf as well as with other components of the polyadenylation machinery. we report here the crystal structure of the hat (half a tpr) domain of murine cstf-77, as well as its c-terminal subdomain. structural and biochemical studies show that the hat domain consists of two subdomains, ha ...200717386263
lc3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of lc3 localization.autophagy is an intracellular bulk degradation system, through which a portion of the cytoplasm is delivered to lysosomes to be degraded. microtuble-associated protein light chain 3 (lc3), a mammalian homolog of yeast atg8, has been used as a specific marker to monitor autophagy. upon induction of autophagy, lc3 is conjugated to phosphatidylethanolamine and targeted to autophagic membranes. therefore, changes in lc3 localization have been used to measure autophagy. however, this method has some ...200717387262
[construction and identification of bait recombinant vector of pgbkt7-tumor necrosis factor-alpha converting enzyme cytoplasmic tail in the yeast two-hybrid system].to construct the bait vector pgbkt7-tacec (cytoplasmic tail of tumor necrosis factor-alpha converting enzyme) of macthmaker gal4 two-hybrid system 3, and to test whether it has self-activation and toxic action.200717393786
a gata2 intronic enhancer confers its pan-endothelia-specific regulation.gata-2, a transcription factor that has been shown to play important roles in multiple organ systems during embryogenesis, has been ascribed the property of regulating the expression of numerous endothelium-specific genes. however, the transcriptional regulatory hierarchy governing gata2 activation in endothelial cells has not been fully explored. here, we document gata-2 endothelial expression during embryogenesis by following gfp expression in gata2-gfp knock-in embryos. using founder transgen ...200717395646
gene expression profiling in equine muscle tissues using mouse cdna microarrays.progress could be achieved by using microarrays to understand metabolic adaptations and disorders in equine muscle in response to exercise.200617402448
def-6, a guanine nucleotide exchange factor for rac1, interacts with the skeletal muscle integrin chain alpha7a and influences myoblast differentiation.integrin alpha7beta1 is the major laminin binding integrin receptor of muscle cells. the alpha7 chain occurs in several splice isoforms, of which alpha7a and alpha7b differ in their intracellular domains only. the fact that the expression of alpha7a and alpha7b is tightly regulated during skeletal muscle development suggests different and distinct roles for both isoforms. however, so far, functional properties and interacting proteins were described for the alpha7b chain only. using a yeast two- ...200717403664
exploring the roles of mus81-eme1/mms4 at perturbed replication forks.cells of all living organisms have evolved complex mechanisms that serve to stabilise, repair and restart stalled, blocked and broken replication forks. the heterodimeric mus81-eme1/mms4 structure-specific endonuclease appears to play an important role(s) in homologous recombination-mediated processing of such perturbed forks. this enzyme has been implicated in the cleavage of stalled and blocked replication forks to initiate recombination, as well as in the processing of recombination intermedi ...200717409028
clic4, skin homeostasis and cutaneous cancer: surprising connections.chloride intracellular channel 4 (clic4) is a putative chloride channel for intracellular organelles. clic4 has biological activities in addition to or because of its channel activity. in keratinocytes, clic4 resides in the mitochondria and cytoplasm, and clic4 gene expression is regulated by p53, tnf-alpha, and c-myc. cytoplasmic clic4 translocates to the nucleus in response to cellular stress conditions including dna damage, metabolic inhibition, senescence, and exposure to certain trophic fac ...200717443730
gazer: gene set analyzer.gene set analyzer (gazer) is a web-based integrated gene set analysis tool covering previously reported parametric and non-parametric models. based on a simulation test for the reported algorithms, we classified and implemented three main statistical methods consisting of the z-statistic, gene permutation and sample permutation for ten gene set categories including gene ontology (go) for human, mouse, rat and yeast. this tool identifies significantly altered gene sets scored by z-statistics and ...200717468122
membrane association is a determinant for substrate recognition by pmt4 protein o-mannosyltransferases.protein o-mannosylation represents an evolutionarily conserved, essential posttranslational modification with immense impact on a variety of cellular processes. in humans, o-mannosylation defects result in walker-warburg syndrome, a severe recessive congenital muscular dystrophy associated with defects in neuronal migration that produce complex brain and eye abnormalities. in mouse and yeasts, loss of o-mannosylation causes lethality. protein o-mannosyltransferases (pmts) initiate the assembly o ...200717470820
chemical sensing of dnt by engineered olfactory yeast strain.with the increasing threat of environmental toxicants including biological and chemical warfare agents, fabricating innovative biomimetic systems to detect these harmful agents is critically important. with the broad objective of developing such a biosensor, here we report the construction of a saccharomyces cerevisiae strain containing the primary components of the mammalian olfactory signaling pathway. in this engineered yeast strain, wif-1alpha, olfactory receptor signaling is coupled to gree ...200717486045
post-translational modification of pou domain transcription factor oct-4 by sumo-1.pou domain transcription factor oct-4 plays a crucial role in maintaining self-renewal and pluripotency of embryonic stem (es) cells in a concentration-dependent manner. however, the molecular mechanism controlling oct-4 levels in es cells remains largely unknown. to explore the molecular mechanism regulating oct-4 function, we constructed a mouse es cell cdna library and performed yeast two-hybrid screening using the pou domain of oct-4 as bait. here, we present novel evidence for oct-4 interac ...200717496161
an n-terminal nucleotide-binding site in vdac1: involvement in regulating mitochondrial function.in a previous study, we presented evidence for the existence of a nucleotide-binding site (nbs) in the n-terminal region of the voltage-dependent anion channel (vdac1). in this study, further localization and possible roles of the proposed vdac1-nbs were investigated using site-directed mutagenesis. the predicated nbs of murine vdac1 (mvdac1) was mutated by replacing two glycine residues with alanines or a conserved lysine residue with a serine. expression of the g21a,g23a- and k20s-mvdac1s in h ...200717503466
gene essentiality, gene duplicability and protein connectivity in human and mouse.it has previously been found that, in yeast, gene essentiality is positively correlated with protein connectivity (number of interaction partners) but negatively correlated with the existence of gene duplicates and that highly connected proteins tend to have a low gene duplicability. using data from human and mouse, we show here that, in mammals, the first of these relationships holds true, but unlike the second relationship in yeast, highly connected mammalian proteins tend to have a high gene ...200717512629
transcription factor modularity in a gene-centered c. elegans core neuronal protein-dna interaction network.transcription regulatory networks play a pivotal role in the development, function, and pathology of metazoan organisms. such networks are comprised of protein-dna interactions between transcription factors (tfs) and their target genes. an important question pertains to how the architecture of such networks relates to network functionality. here, we show that a caenorhabditis elegans core neuronal protein-dna interaction network is organized into two tf modules. these modules contain tfs that bi ...200717513831
structure of the munc18c/syntaxin4 n-peptide complex defines universal features of the n-peptide binding mode of sec1/munc18 proteins.sec1/munc18 proteins (sm proteins) bind to soluble nsf attachment protein receptors (snares) and play an essential role in membrane fusion. divergent modes of regulation have been proposed for different sm proteins indicating that they can either promote or inhibit snare assembly. this is in part because of discrete modes of binding that have been described for various sm/snare complexes. one mode suggests that sm proteins bind only to syntaxins (stx) preventing snare assembly, whereas in anothe ...200717517664
indelscan: a web server for comparative identification of species-specific and non-species-specific insertion/deletion events.insertion and deletion (indel) events usually have dramatic effects on genome structure and gene function. species-specific indels have been demonstrated to be associated with species-unique traits. currently, indel identifications mainly rely on pair-wise sequence alignments (the 'pair-wise indels'), which suffer lack of discrimination of species specificity and insertion versus deletion. also, there is no freely accessible web server for genome-wide identification of indels. therefore, we deve ...200717517762
exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model.candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. th1 cytokines such as interleukin-2 (il-2), gamma interferon (ifn-gamma), and tumor necrosis factor alpha (tnf-alpha), which are induced by macrophage il-12, are critical to resistance against systemic candidiasis, while th2 cytokines such as il-4 and il-5 are less critical. farnesol is a quorum-sensing molecule produced by c. albicans that controls the formation of mycelia but is ...200717517874
sirt2 deacetylates foxo3a in response to oxidative stress and caloric restriction.the sirtuin family of nicotinamide adenine dinucleotide-dependent (nad) deacetylases plays an important role in aging and metabolic regulation. in yeast, the sir2 gene and its homolog hst2 independently mediate the action of caloric restriction on lifespan extension. the mammalian sir2 ortholog, sirt1, is up-regulated by caloric restriction and deacetylates a variety of substrates, including histones and the forkhead box o (foxo) transcription factors. the mammalian ortholog of hst2, sirt2, was ...200717521387
beta-cryptoxanthin, a novel natural rar ligand, induces atp-binding cassette transporters in macrophages.despite its serious adverse effects, recent accumulating evidence suggests that a physiological retinoic acid receptor (rar) agonist, all-trans retinoic acid (atra), exhibits preventive effects on atherogenesis. therefore, the present study was designed to explore novel natural rar ligands with anti-atherogenic effects in order to identify and develop a drug without severe side effects. among xanthophylls and carotenoids studied, beta-cryptoxanthin and lutein exhibited rar ligand activity in yea ...200717521617
huntingtin facilitates dynein/dynactin-mediated vesicle transport.cytoplasmic dynein is a multisubunit microtubule motor complex that, together with its activator, dynactin, drives vesicular cargo toward the minus ends of microtubules. huntingtin (htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be involved in vesicular transport. in this study, we demonstrate through yeast two-hybrid and affinity chromatography assays that htt and dynein intermediate chain interact directly; endogenous htt and dynein co-immu ...200717548833
resveratrol is a class ia phosphoinositide 3-kinase inhibitor.resveratrol, a polyphenol found in fruits, possesses chemopreventive and chemotherapeutic properties and has been shown to increase lifespan in yeast and metazoans, including mice. genetic evidence and in vitro enzymatic measurements indicate that the deacetylase sir2/sirt1, an enzyme promoting stress resistance and aging, is the target of resveratrol. similarly, down-regulation of insulin-like pathways, of which pi3k (phosphoinositide 3-kinase) is a key mediator, promotes longevity and is an at ...200717550345
linking physiology and transcriptional profiles by quantitative predictive models.a methodology for the construction of quantitative, predictive models of physiology from transcriptional profiles is presented. the method utilizes partial least squares (pls) regression properly modified to allow gene pre-selection based on their signal-to-noise ratio (snr). the final set of genes is obtained from a consensus ranking of genes across several thousand trials, each carried out with a different set of training samples. the method was tested with transcriptional data from a large-sc ...200717551988
a comparison of the pulmonary inflammatory potential of different components of yeast cell wall.1-->3-beta-glucan has been associated with pulmonary inflammation induced by exposure to fungal or yeast cell wall dust. 1-->3-beta-glucan is the major cell wall component of yeast or fungi. however, the yeast cell wall contains several other components besides 1-->3-beta-glucans, such as mannan and chitin. few studies evaluated the contribution of these other cell wall components to pulmonary inflammation. the present study compares a crude particulate yeast cell wall preparation (zymosan a) to ...200717558806
gamma-tubulin-like molecules in the mouse duodenal epithelium.a mouse monoclonal antibody (g9, horio et al. in cell motil cytoskel 44:284-295, 1999) that was raised against the gamma-tubulin from a fission yeast, schizosaccharomyces pombe, showed a unique staining in the mouse small intestine. similar to another anti-gamma-tubulin antibody that is commercially available, g9 showed typical dot-like staining corresponding to the microtubule-organizing center in the free cells of the epithelium and the connective tissue under it. in addition, g9 stained the c ...200717562068
pias3 interacts with atf1 and regulates the human ferritin h gene through an antioxidant-responsive element.gene transcription is coordinately regulated by the balance between activation and repression mechanisms in response to various external stimuli. ferritin, composed of h and l subunits, is the major intracellular iron storage protein involved in iron homeostasis. we previously identified an enhancer, termed antioxidant-responsive element (are), in the human ferritin h gene and its respective transcriptional activators including nrf2 and jund. here we found that atf1 (activating transcription fac ...200717565989
finding plk3.polo-like kinases (plks) are a highly conserved family of kinases found in flies, yeast and vertebrates. plks derive their name from homology to the gene product of polo, a protein kinase first identified in drosophila. three polo-like kinases have been identified in vertebrates: plk1, plk2 and plk3. studies on plk1 have revealed a great deal of information on its multiple functions, however plk2 and plk3 functions have not been fully explored. in this perspective we discuss recent work on plk3 ...200717568195
using indirect protein interactions for the prediction of gene ontology functions.protein-protein interaction has been used to complement traditional sequence homology to elucidate protein function. most existing approaches only make use of direct interactions to infer function, and some have studied the application of indirect interactions for functional inference but are unable to improve prediction performance. we have previously proposed an approach, fs-weighted averaging, which uses topological weighting and level-2 indirect interactions (protein pairs connected via two ...200717570151
generation of a transgenic model to address regulation and function of the human neurokinin 1 receptor (nk1r).we have generated mouse transgenic lines using yeast artificial chromosome (yac) technology which demonstrate expression from the human nk1 receptor (nk1r) locus. we introduced a 380 kb fragment encompassing the human nk1r gene and flanking regions which we hoped would recapitulate the expected endogenous expression of the human gene. to visualise this expression the nk1 locus co-expresses the green fluorescence protein gene (gfp) under the control of an internal ribosome entry site (ires) seque ...200717576012
organization of chromatin and histone modifications at a transcription site.according to the transcription factory model, localized transcription sites composed of immobilized polymerase molecules transcribe chromatin by reeling it through the transcription site and extruding it to form a surrounding domain of recently transcribed decondensed chromatin. although transcription sites have been identified in various cells, surrounding domains of recently transcribed decondensed chromatin have not. we report evidence that transcription sites associated with a tandem gene ar ...200717576795
the crystal structure of mouse exo70 reveals unique features of the mammalian exocyst.the exocyst is a eukaryotic tethering complex necessary for the fusion of exocytic vesicles with the plasma membrane. its function in vivo is tightly regulated by interactions with multiple small gtpases. exo70, one of the eight subunits of the exocyst, is important for the localization of the exocyst to the plasma membrane. it interacts with tc10 and rho3 gtpases in mammals and yeast, respectively, and has been shown recently to bind to the actin-polymerization complex arp2/3. here, we present ...200717583731
mapping the ruthenium red-binding site of the voltage-dependent anion channel-1.we have previously shown that ruthenium red (rur) binds to the voltage-dependent anion channel (vdac) in the outer mitochondrial membrane, decreasing channel conductance and protecting against apoptotic cell death. in this report, we define the murine and yeast vdac1 amino acid residues involved in the interaction with rur. binding of rur to bilayer-reconstituted mvdac1 and the resulting channel closure was inhibited upon mutation of specific vdac1 residues. rur protection against cell death, as ...200817590433
frataxin is essential for extramitochondrial fe-s cluster proteins in mammalian tissues.friedreich ataxia, the most common recessive ataxia, is caused by the deficiency of the mitochondrial protein frataxin (fxn), an iron chaperone involved in the assembly of fe-s clusters (isc). in yeast, mitochondria play a central role for all fe-s proteins, independently of their subcellular localization. in mammalian cells, this central role of mitochondria remains controversial as an independent cytosolic isc assembly machinery has been suggested. in the present work, we show that three extra ...200717597094
dual e1 activation systems for ubiquitin differentially regulate e2 enzyme charging.modification of proteins with ubiquitin or ubiquitin-like proteins (ubls) by means of an e1-e2-e3 cascade controls many signalling networks. ubiquitin conjugation involves adenylation and thioesterification of the carboxy-terminal carboxylate of ubiquitin by the e1-activating enzyme ube1 (uba1 in yeast), followed by ubiquitin transfer to an e2-conjugating enzyme through a transthiolation reaction. charged e2s function with e3s to ubiquitinate substrates. it is currently thought that ube1/uba1 is ...200717597759
deletion of the high-affinity camp phosphodiesterase encoded by pde2 affects stress responses and virulence in candida albicans.previously, we have shown that pde2 is required for hyphal development and cell wall integrity in candida albicans. in the present study, we have investigated the effects of its deletion by genome-wide transcriptome profiling. changes in expression levels of genes involved in metabolism, transcription, protein and nucleic acids synthesis, as well as stress responses, cell wall and membrane biogenesis, adherence and virulence have been observed. by comparing these changes with previously reported ...200717614954
gnl3l inhibits activity of estrogen-related receptor gamma by competing for coactivator binding.guanine nucleotide binding protein-like 3 (gnl3l) is the closest homologue of a stem cell-enriched factor nucleostemin in vertebrates. they share the same yeast orthologue, grn1p, but only gnl3l can rescue the growth-deficient phenotype in grn1-null yeasts. to determine the unique function of gnl3l, we identified estrogen-related receptor gamma (errgamma) as a gnl3l-specific binding protein. gnl3l and errgamma are coexpressed in the eye, kidney and muscle, and co-reside in the nucleoplasm. the i ...200717623774
heterochromatin is refractory to gamma-h2ax modification in yeast and mammals.double-strand break (dsb) damage in yeast and mammalian cells induces the rapid atm (ataxia telangiectasia mutated)/atr (ataxia telangiectasia and rad3 related)-dependent phosphorylation of histone h2ax (gamma-h2ax). in budding yeast, a single endonuclease-induced dsb triggers gamma-h2ax modification of 50 kb on either side of the dsb. the extent of gamma-h2ax spreading does not depend on the chromosomal sequences. dna resection after dsb formation causes the slow, progressive loss of gamma-h2ax ...200717635934
monoubiquitylation of h2a.z distinguishes its association with euchromatin or facultative heterochromatin.h2a.z is a histone h2a variant that is essential for viability in organisms such as tetrahymena thermophila, drosophila melanogaster, and mice. in saccharomyces cerevisiae, loss of h2a.z is tolerated, but proper regulation of gene expression is affected. genetics and genome-wide localization studies show that yeast h2a.z physically localizes to the promoters of genes and functions in part to protect active genes in euchromatin from being silenced by heterochromatin spreading. to date, the functi ...200717636032
ledgf/p75 functions downstream from preintegration complex formation to effect gene-specific hiv-1 integration.ledgf/p75 directly interacts with lentiviral integrase proteins and can modulate their enzymatic activities and chromosomal association. a novel genetic knockout model was established that allowed us for the first time to analyze hiv-1 integration in the absence of ledgf/p75 protein. supporting a crucial role for the cofactor in viral replication, hiv-1 vector integration and reporter gene expression were significantly reduced in ledgf-null cells. yet, integrase processed the viral cdna termini ...200717639082
dopaminergic signaling and striatal neurodegeneration in huntington's disease.huntington's disease (hd) is a neurodegenerative disorder caused by polyglutamine (polyq) expansion in huntingtin protein (htt). polyq expansion in htt(exp) causes selective degeneration of striatal medium spiny neurons (msns) in hd patients. striatal msn neurons receive glutamatergic input from the cortex and dopaminergic input from the substantia nigra. in previous studies with the yeast artificial chromosome (yac128) transgenic hd mouse model, we established a connection between glutamate rec ...200717652581
opinion: alternative views of amp-activated protein kinase.genes most closely related to adenosine monophosphate (amp)-activated protein kinase, including sad kinases and par-1 regulate cell polarity, although amp-activated protein kinase (ampk) modulates cellular energy status. lkb1 (par-4) is required for normal activation of ampk in the liver and also regulates cell polarity. ampk is proposed to inhibit energy consuming activity while initiating energy producing activity during energy limitation. demonstration that metformin, a common drug for type 2 ...200717652778
pttg is a secretory protein in human pituitary adenomas and in mouse pituitary tumor cell lines.the pituitary tumor-transforming gene (pttg) is a homolog of yeast securin, which arrests the activation of separin to induce sister chromatid separation in the transition from metaphase to anaphase. pituitary tumor-transforming gene is also known to induce angiogenesis during pituitary tumorigenesis. it has not been clarified whether pttg functions as a cytoplasmic or a nuclear protein. our immunohistochemical study indicated that pttg is localized in the cytoplasm of pituitary tumor cells. in ...200717652795
identification and characterization of a novel protein isoc2 that interacts with p16ink4a.p16(ink4a) is a multiple tumor suppressor, playing an important role in proliferation and tumorigenesis. to screen the p16(ink4a)-associated proteins, we performed a yeast two-hybrid assay and identified a novel protein isochorismatase domain containing 2 (isoc2). isoc2 conserves in different species, and encodes 205 and 210 amino acids in human and mouse, respectively. the expression of isoc2 in mouse is universal but predominantly in uterus, stomach, and urinary tract system. interaction betwe ...200717658461
aryl hydrocarbon receptor ligand activity of polycyclic aromatic ketones and polycyclic aromatic quinones.polycyclic aromatic ketones (paks) and polycyclic aromatic quinones (paqs) are oxygenated polycyclic aromatic hydrocarbons (pahs), and reports about the aryl hydrocarbon receptor (ahr) ligand activities of these compounds are few. in this study, activation of ahr by 41 polycyclic aromatic compounds (pacs), focusing especially on paks and paqs, was determined by measuring beta-galactosidase activity from a reporter plasmid in yeast engineered to express human ahr and the ahr nuclear translocator ...200717665676
highly efficient gene delivery for bladder cancers by intravesically administered replication-competent retroviral vectors.in an attempt to improve viral delivery of potentially therapeutic genes via an intravesical route, we have recently developed murine leukemia virus-based replication-competent retrovirus (rcr) vectors.200717671137
ceftezole, a cephem antibiotic, is an alpha-glucosidase inhibitor with in vivo anti-diabetic activity.using a high throughput-compatible assay to screen for potential alpha-glucosidase inhibitors, we found that the beta-lactam antibiotic ceftezole exhibited potent alpha-glucosidase inhibitory activity. in in vitro alpha-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast alpha-glucosidase with a ki value of 5.78 x 10(-7) m when the enzyme mixture was pretreated with ceftezole. using an in vivo streptozotocin-induced mouse model, we confirmed that blood ...200717671744
orthology and functional conservation in eukaryotes.in recent years, it has become clear that all of the organisms on the earth are related to each other in ways that can be documented by molecular sequence comparison. in this review, we focus on the evolutionary relationships among the proteins of the eukaryotes, especially those that allow inference of function from one species to another. data and illustrations are derived from specific comparison of eight species: homo sapiens, mus musculus, arabidopsis thaliana, caenorhabditis elegans, danio ...200717678444
htra2 regulates beta-amyloid precursor protein (app) metabolism through endoplasmic reticulum-associated degradation.alzheimer disease-associated beta-amyloid peptide is generated from its precursor protein app. by using the yeast two-hybrid assay, here we identified htra2/omi, a stress-responsive chaperone-protease as a protein binding to the n-terminal cysteinerich region of app. htra2 coimmunoprecipitates exclusively with immature app from cell lysates as well as mouse brain extracts and degrades app in vitro. a subpopulation of htra2 localizes to the cytosolic side of the endoplasmic reticulum (er) membran ...200717684015
meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome.fertility requires successful chromosome segregation in meiosis, which in most sexual organisms depends on the formation of appropriately placed crossovers. the nonrandom genome-wide distributions of meiotic recombination events have been examined at the molecular level experimentally in yeast and by inference from linkage disequilibrium patterns in humans. thus far, no method has existed for pinpointing sites of crossing-over on a genome-wide scale in an experimentally tractable animal whose ge ...200717690247
mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.in mammalian meiosis, homologous chromosome synapsis is coupled with recombination. as in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. we report that the mouse ortholog (trip13) of pachytene checkpoint 2 (pch2), an essential component of the synapsis checkpoint in saccharomyces cerevisiae and caenorhabditis elegans, is required for completion of meiosis in both sexes. trip13-deficient mice exhibit spermatocyte death in pachynema and loss of ...200717696610
effects of water-soluble low-molecular-weight beta-1, 3-d-glucan (branch beta-1, 6) isolated from aureobasidium pullulans 1a1 strain black yeast on restraint stress in mice.it is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. it has been reported that glucocorticoids suppress natural killer (nk) activity and interleukin (il)-1 production and, on the other hand, that il-1 and il-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. moreover, it has been reported that il-12 plays a central role in the ...200717725857
the dna polymerase gamma y955c disease variant associated with peo and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine.mitochondrial dna is replicated and repaired by dna polymerase gamma (pol gamma), encoded by the polg gene. the y955c substitution in polg leads to autosomal dominant progressive external ophthalmoplegia (peo) with other severe phenotypes. peo patients with this mutation can further develop parkinsonism or premature ovarian failure. mouse and yeast models with this mutation show enhanced amounts of oxidative lesions and increased mtdna damage. in dna pol gamma, tyr955 plays a critical role in ca ...200717725985
the checkpoint saccharomyces cerevisiae rad9 protein contains a tandem tudor domain that recognizes dna.dna damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. at the site of dna damage, 'mediator' proteins are in charge of recruiting 'signal transducers' to molecules 'sensing' the damage. budding yeast rad9, fission yeast crb2 and metazoan 53bp1 are presented as mediators involved in the activation of checkpoint kinases. here we show that, despite low sequence conservation, rad9 exhibits a tandem tudor domain structurally cl ...200717726056
wide-scale analysis of human functional transcription factor binding reveals a strong bias towards the transcription start site.transcription factors (tf) regulate expression by binding to specific dna sequences. a binding event is functional when it affects gene expression. functionality of a binding site is reflected in conservation of the binding sequence during evolution and in over represented binding in gene groups with coherent biological functions. functionality is governed by several parameters such as the tf-dna binding strength, distance of the binding site from the transcription start site (tss), dna packing, ...200717726537
interactions of recombinant mouse erythrocyte transglutaminase with membrane skeletal proteins.transglutaminases (tgs) are a family of enzymes that catalyze the formation of covalent gamma-glutamyl-epsilon-lysine crosslinks between glutamine (q) acyl-donors and lysine (k) acyl-acceptors. here, we report the cdna cloning of a tg from mouse reticulocytes, its 4.6-kb message size and high-yield synthesis of recombinant tg in yeast cultures. its activity was assayed by crosslinking the amine of monodansylcadaverine (dc) onto casein and inside-out vesicles of erythrocytes. the latter contain t ...200717763875
mutation in mouse hei10, an e3 ubiquitin ligase, disrupts meiotic crossing over.crossing over during meiotic prophase i is required for sexual reproduction in mice and contributes to genome-wide genetic diversity. here we report on the characterization of an n-ethyl-n-nitrosourea-induced, recessive allele called mei4, which causes sterility in both sexes owing to meiotic defects. in mutant spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. mutant oocytes have a similar chromosomal p ...200717784788
exonuclease-1 deletion impairs dna damage signaling and prolongs lifespan of telomere-dysfunctional mice.exonuclease-1 (exo1) mediates checkpoint induction in response to telomere dysfunction in yeast, but it is unknown whether exo1 has similar functions in mammalian cells. here we show that deletion of the nuclease domain of exo1 reduces accumulation of dna damage and dna damage signal induction in telomere-dysfunctional mice. exo1 deletion improved organ maintenance and lifespan of telomere-dysfunctional mice but did not increase chromosomal instability or cancer formation. deletion of exo1 also ...200717803909
generation of a prophylactic melanoma vaccine using whole recombinant yeast expressing mart-1.malignant melanoma is a potentially deadly form of skin cancer and people at high-risk of developing melanoma will benefit from effective preventive intervention. yeast can be used as an efficient vehicle of antigen loading and immunostimulation. saccharomyces cerevisiae is not pathogenic to humans and can be easily engineered to express specific antigens. in this study, we have developed a melanoma vaccine using a yeast-based platform expressing a full-length melanocyte/melanoma protein to inve ...200717845213
bif-1 interacts with beclin 1 through uvrag and regulates autophagy and tumorigenesis.autophagy is an evolutionarily conserved 'self-eating' process. although the genes essential for autophagy (named atg) have been identified in yeast, the molecular mechanism of how atg proteins control autophagosome formation in mammalian cells remains to be elucidated. here, we demonstrate that bif-1 (also known as endophilin b1) interacts with beclin 1 through ultraviolet irradiation resistance-associated gene (uvrag) and functions as a positive mediator of the class iii pi(3) kinase (pi(3)kc3 ...200717891140
ganp suppresses dna recombination, measured by direct-repeat beta-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells.immunoglobulin v-region somatic hypermutation and c-region class-switch recombination are initiated by activation-induced cytidine deaminase (aid) in b-cells. aid-induced dna damage at the immunoglobulin s-region is known to be repaired by non-homologous end-joining, but repair mechanisms at the v-region remain to be elucidated. in saccharomyces cerevisiae, dna homologous recombination is regulated by the expression of sac3, involved in actin assembly, cell cycle transition and mrna metabolism. ...200717903179
o-mannosyltransferase 1 in aspergillus fumigatus (afpmt1p) is crucial for cell wall integrity and conidium morphology, especially at an elevated temperature.protein o-mannosyltransferases initiate o mannosylation of secretory proteins, which are of fundamental importance in eukaryotes. in this study, the pmt gene family of the human fungal pathogen aspergillus fumigatus was identified and characterized. unlike the case in saccharomyces cerevisiae, where the pmt family is highly redundant, only one member of each pmt subfamily, namely, afpmt1, afpmt2, and afpmt4, is present in a. fumigatus. mutants with a deletion of afpmt1 are viable. in vitro and i ...200717905922
mtbp haploinsufficiency in mice increases tumor metastasis.mdm2 inhibits the function of the p53 tumor suppressor. mdm2 is overexpressed in many tumors with wild-type p53 suggesting an alternate mechanism of loss of p53 activity in tumors. an mdm2-binding protein (mtbp) was identified using a yeast two-hybrid screen. in tissue culture, mtbp inhibits mdm2 self-ubiquitination, leading to stabilization of mdm2 and increased degradation of p53. to address the role of mtbp in the regulation of the p53 pathway in vivo, we deleted the mtbp gene in mice. homozy ...200817906694
the ajuba lim domain protein is a corepressor for snag domain mediated repression and participates in nucleocytoplasmic shuttling.the snag repression domain is comprised of a highly conserved 21-amino acid sequence, is named for its presence in the snail/growth factor independence-1 class of zinc finger transcription factors, and is present in a variety of proto-oncogenic transcription factors and developmental regulators. the prototype snag domain containing oncogene, growth factor independence-1, is responsible for the development of t cell thymomas. the snail proteins also encode the snag domain and play key roles in ep ...200717909014
mammalian sir2 homolog sirt3 regulates global mitochondrial lysine acetylation.homologs of the saccharomyces cerevisiae sir2 protein, sirtuins, promote longevity in many organisms. studies of the sirtuin sirt3 have so far been limited to cell culture systems. here, we investigate the localization and function of sirt3 in vivo. we show that endogenous mouse sirt3 is a soluble mitochondrial protein. to address the function and relevance of sirt3 in the regulation of energy metabolism, we generated and phenotypically characterized sirt3 knockout mice. sirt3-deficient animals ...200717923681
the intercalated disk protein, mxinalpha, is capable of interacting with beta-catenin and bundling actin filaments [corrected].targeted deletion of mxinalpha results in cardiac hypertrophy and cardiomyopathy with conduction defects (gustafson-wagner, e., sinn, h. w., chen, y.-l., wang, d.-z., reiter, r. s., lin, j. l.-c., yang, b., williamson, r. a., chen, j. n., lin, c.-i., and lin, j. j.-c. (2007) am. j. physiol. 293, h2680-h2692). to understand the underlying mechanisms leading to such cardiac defects, the functional domains of mxinalpha and its interacting proteins were investigated. interaction studies using co-imm ...200717925400
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